                         SEQUENCE LISTING

<110>  Adamed Sp. z o.o.
 
<120>  Anticancer conjugate

<130>  P129 02 PL

<160>  23    

<170>  PatentIn version 3.5

<210>  1
<211>  281
<212>  PRT
<213>  Homo sapiens

<300>
<308>  GenBank/P50591
<309>  1996-10-01
<313>  (1)..(281)

<400>  1

Met Ala Met Met Glu Val Gln Gly Gly Pro Ser Leu Gly Gln Thr Cys 
1               5                   10                  15      


Val Leu Ile Val Ile Phe Thr Val Leu Leu Gln Ser Leu Cys Val Ala 
            20                  25                  30          


Val Thr Tyr Val Tyr Phe Thr Asn Glu Leu Lys Gln Met Gln Asp Lys 
        35                  40                  45              


Tyr Ser Lys Ser Gly Ile Ala Cys Phe Leu Lys Glu Asp Asp Ser Tyr 
    50                  55                  60                  


Trp Asp Pro Asn Asp Glu Glu Ser Met Asn Ser Pro Cys Trp Gln Val 
65                  70                  75                  80  


Lys Trp Gln Leu Arg Gln Leu Val Arg Lys Met Ile Leu Arg Thr Ser 
                85                  90                  95      


Glu Glu Thr Ile Ser Thr Val Gln Glu Lys Gln Gln Asn Ile Ser Pro 
            100                 105                 110         


Leu Val Arg Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly 
        115                 120                 125             


Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu 
    130                 135                 140                 


Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly 
145                 150                 155                 160 


His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile 
                165                 170                 175     


His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe 
            180                 185                 190         


Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln 
        195                 200                 205             


Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys 
    210                 215                 220                 


Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr 
225                 230                 235                 240 


Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile 
                245                 250                 255     


Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala 
            260                 265                 270         


Ser Phe Phe Gly Ala Phe Leu Val Gly 
        275                 280     


<210>  2
<211>  150
<212>  PRT
<213>  Homo sapiens

<300>
<308>  GenBank: AAB59402.1
<309>  2001-01-08
<313>  (24)..(173)

<400>  2

Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln 
        35                  40                  45              


Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe 
    50                  55                  60                  


Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 
65                  70                  75                  80  


Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu 
                85                  90                  95      


Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 
            100                 105                 110         


Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu 
        115                 120                 125             


Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 
    130                 135                 140                 


Ala Glu Ile Met Arg Ser 
145                 150 


<210>  3
<211>  124
<212>  PRT
<213>  Homo sapiens

<300>
<308>  GenBank/AAM28885.1
<309>  2002-05-16
<313>  (2)..(125)

<400>  3

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala 
        115                 120                 


<210>  4
<211>  263
<212>  PRT
<213>  Homo sapiens

<300>
<308>  PDB/1EKUA
<309>  2008-09-24
<313>  (2)..(264)

<400>  4

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile Asp Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Phe Ser Thr Glu Glu Gln Gln Glu Gly 
        115                 120                 125             


Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly 
    130                 135                 140                 


His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys 
145                 150                 155                 160 


Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val 
                165                 170                 175     


Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile 
            180                 185                 190         


Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe 
        195                 200                 205             


Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr 
    210                 215                 220                 


Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile 
225                 230                 235                 240 


Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg Lys 
                245                 250                 255     


Arg Ser Gln Met Leu Phe Arg 
            260             


<210>  5
<211>  351
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  none

<400>  5

Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln 
        35                  40                  45              


Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe 
    50                  55                  60                  


Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 
65                  70                  75                  80  


Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu 
                85                  90                  95      


Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 
            100                 105                 110         


Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu 
        115                 120                 125             


Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 
    130                 135                 140                 


Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser 
145                 150                 155                 160 


Leu Arg Ser Lys Glu Gly Gly Gly Gly Ser Pro Leu Gly Leu Ala Gly 
                165                 170                 175     


Arg Val Val Arg Ser Gly Gly Gly Gly Ser Glu Lys Ser Arg Leu Ser 
            180                 185                 190         


Glu Gln Leu Asn Thr Ser Leu Ser Phe Ser Arg Met Ile Glu Ala Arg 
        195                 200                 205             


Val Val Glu Trp Ala Cys Pro Ser Tyr Lys Lys Glu Lys Leu Tyr Leu 
    210                 215                 220                 


Thr Ile Arg Gln Phe Tyr Phe Arg Val Ala Leu Ile Ser Asp Glu Lys 
225                 230                 235                 240 


Met Leu Pro Thr Glu Thr Val Gly Val Gly Gln Ile Val Cys Ala Glu 
                245                 250                 255     


Leu Asp Asn Leu Gln Gln Tyr Leu Glu Thr Tyr Phe Lys Asp Leu Leu 
            260                 265                 270         


Thr Glu Asp Trp Ala Ala Ser Ser Asp Lys Thr Ser Phe Leu Asn Phe 
        275                 280                 285             


Ile Gln Gln Ile Met Glu His Leu Val Pro Ile Thr Glu Ala Lys Gln 
    290                 295                 300                 


Phe Gln Asn Gly Phe Glu Glu Gln Pro Phe Gly Phe Asp His Arg Asp 
305                 310                 315                 320 


Lys Leu Cys Ser Phe Leu Ser Ile Arg Arg Met Gln Ala Leu Leu Met 
                325                 330                 335     


Leu Thr Arg Arg Ser Gly Leu Ser His Thr Gln Pro Leu Asp Cys 
            340                 345                 350     


<210>  6
<211>  166
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  none

<300>
<302>  consensus human leukocyte interferon
<310>  US4695623
<311>  1983-12-12
<312>  1987-09-22

<400>  6

Ser Asp Leu Pro Gln Thr His Ser Leu Gly Asn Arg Arg Ala Leu Ile 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Pro Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Asp Gly Asn Gln Phe 
        35                  40                  45              


Gln Lys Ala Gln Ala Ile Ser Val Leu His Glu Met Ile Gln Gln Thr 
    50                  55                  60                  


Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Ser 
65                  70                  75                  80  


Leu Leu Glu Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu 
                85                  90                  95      


Glu Ala Cys Val Ile Gln Glu Val Gly Val Glu Glu Thr Pro Leu Met 
            100                 105                 110         


Asn Val Asp Ser Ile Leu Ala Val Lys Lys Tyr Phe Gln Arg Ile Thr 
        115                 120                 125             


Leu Tyr Leu Thr Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val 
    130                 135                 140                 


Arg Ala Glu Ile Met Arg Ser Phe Ser Ile Ser Thr Asn Leu Gln Glu 
145                 150                 155                 160 


Arg Leu Arg Arg Lys Glu 
                165     


<210>  7
<211>  345
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a subunit 2b of human interferon alpha and a cleavage 
       site recognized by metalloprotease MMP and urokinase uPA.

<400>  7

Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln 
        35                  40                  45              


Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe 
    50                  55                  60                  


Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 
65                  70                  75                  80  


Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu 
                85                  90                  95      


Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 
            100                 105                 110         


Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu 
        115                 120                 125             


Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 
    130                 135                 140                 


Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser 
145                 150                 155                 160 


Leu Arg Ser Lys Glu Pro Leu Gly Leu Ala Gly Arg Val Val Arg Pro 
                165                 170                 175     


Leu Gly Leu Ala Gly Arg Val Val Arg Val Ala Ala His Ile Thr Gly 
            180                 185                 190         


Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu 
        195                 200                 205             


Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly 
    210                 215                 220                 


His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile 
225                 230                 235                 240 


His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe 
                245                 250                 255     


Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln 
            260                 265                 270         


Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys 
        275                 280                 285             


Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr 
    290                 295                 300                 


Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile 
305                 310                 315                 320 


Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala 
                325                 330                 335     


Ser Phe Phe Gly Ala Phe Leu Val Gly 
            340                 345 


<210>  8
<211>  347
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a subunit 2b of human interferon alpha and a cleavage 
       site recognized by metalloprotease MMP and urokinase uPA.

<400>  8

Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr 
1               5                   10                  15      


Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile 
            20                  25                  30          


Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu 
        35                  40                  45              


His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr 
    50                  55                  60                  


Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn 
65                  70                  75                  80  


Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser 
                85                  90                  95      


Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp 
            100                 105                 110         


Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile 
        115                 120                 125             


Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu 
    130                 135                 140                 


His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu 
145                 150                 155                 160 


Val Gly Pro Leu Gly Leu Ala Gly Arg Val Val Arg Pro Leu Gly Leu 
                165                 170                 175     


Ala Gly Arg Val Val Arg Cys Asp Leu Pro Gln Thr His Ser Leu Gly 
            180                 185                 190         


Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser Leu 
        195                 200                 205             


Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu Glu 
    210                 215                 220                 


Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His Glu 
225                 230                 235                 240 


Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala 
                245                 250                 255     


Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln 
            260                 265                 270         


Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val Thr 
        275                 280                 285             


Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr 
    290                 295                 300                 


Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys 
305                 310                 315                 320 


Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu Ser 
                325                 330                 335     


Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu 
            340                 345         


<210>  9
<211>  352
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a subunit 2b of human interferon alpha, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and a linker 
       for pegylation.

<400>  9

Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln 
        35                  40                  45              


Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe 
    50                  55                  60                  


Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 
65                  70                  75                  80  


Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu 
                85                  90                  95      


Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 
            100                 105                 110         


Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu 
        115                 120                 125             


Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 
    130                 135                 140                 


Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser 
145                 150                 155                 160 


Leu Arg Ser Lys Glu Pro Leu Gly Leu Ala Gly Arg Val Val Arg Ala 
                165                 170                 175     


Ser Gly Cys Gly Pro Glu Pro Leu Gly Leu Ala Gly Arg Val Val Arg 
            180                 185                 190         


Val Ala Ala His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr Leu Ser 
        195                 200                 205             


Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile Asn Ser 
    210                 215                 220                 


Trp Glu Ser Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu His Leu 
225                 230                 235                 240 


Arg Asn Gly Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr Ile Tyr 
                245                 250                 255     


Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn Thr Lys 
            260                 265                 270         


Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro 
        275                 280                 285             


Asp Pro Ile Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp Ser Lys 
    290                 295                 300                 


Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile Phe Glu 
305                 310                 315                 320 


Leu Lys Glu Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu His Leu 
                325                 330                 335     


Ile Asp Met Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu Val Gly 
            340                 345                 350         


<210>  10
<211>  353
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a subunit 2b of human interferon alpha, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and a linker 
       for pegylation.

<400>  10

Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr Leu 
1               5                   10                  15      


Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile Asn 
            20                  25                  30          


Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu His 
        35                  40                  45              


Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr Ile 
    50                  55                  60                  


Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn Thr 
65                  70                  75                  80  


Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr 
                85                  90                  95      


Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp Ser 
            100                 105                 110         


Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile Phe 
        115                 120                 125             


Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu His 
    130                 135                 140                 


Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu Val 
145                 150                 155                 160 


Gly Pro Leu Gly Leu Ala Gly Arg Val Val Arg Ala Ser Gly Cys Gly 
                165                 170                 175     


Pro Glu Pro Leu Gly Leu Ala Gly Arg Val Val Arg Cys Asp Leu Pro 
            180                 185                 190         


Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln 
        195                 200                 205             


Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe 
    210                 215                 220                 


Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr 
225                 230                 235                 240 


Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser 
                245                 250                 255     


Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe 
            260                 265                 270         


Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile 
        275                 280                 285             


Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile 
    290                 295                 300                 


Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu 
305                 310                 315                 320 


Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met 
                325                 330                 335     


Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys 
            340                 345                 350         


Glu 
    


<210>  11
<211>  300
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma and a cleavage site
       recognized by metalloprotease MMP and urokinase uPA.

<400>  11

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Pro Leu Gly Leu 
        115                 120                 125             


Ala Gly Arg Val Val Arg Glu Arg Gly Pro Gln Arg Val Ala Ala His 
    130                 135                 140                 


Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser 
145                 150                 155                 160 


Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser 
                165                 170                 175     


Arg Ser Gly His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu 
            180                 185                 190         


Leu Val Ile His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr 
        195                 200                 205             


Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln 
    210                 215                 220                 


Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu 
225                 230                 235                 240 


Leu Met Lys Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr 
                245                 250                 255     


Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn 
            260                 265                 270         


Asp Arg Ile Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp 
        275                 280                 285             


His Glu Ala Ser Phe Phe Gly Ala Phe Leu Val Gly 
    290                 295                 300 


<210>  12
<211>  307
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma and a cleavage site
       recognized by metalloprotease MMP and urokinase uPA.

<400>  12

Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly 
1               5                   10                  15      


Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu 
            20                  25                  30          


Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe 
        35                  40                  45              


Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys 
    50                  55                  60                  


Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu 
65                  70                  75                  80  


Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr 
                85                  90                  95      


Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg 
            100                 105                 110         


Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr 
        115                 120                 125             


Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser 
    130                 135                 140                 


Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe 
145                 150                 155                 160 


Gly Ala Phe Leu Val Gly Gly Gly Ser Pro Leu Gly Leu Ala Gly Arg 
                165                 170                 175     


Val Val Arg Gly Gly Gly Ser Gln Asp Pro Tyr Val Lys Glu Ala Glu 
            180                 185                 190         


Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn 
        195                 200                 205             


Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp 
    210                 215                 220                 


Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe 
225                 230                 235                 240 


Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile 
                245                 250                 255     


Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg 
            260                 265                 270         


Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val 
        275                 280                 285             


Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser 
    290                 295                 300                 


Pro Ala Ala 
305         


<210>  13
<211>  310
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and 
       glycine-serine linkers.

<400>  13

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Gly Ser Gly Gly 
        115                 120                 125             


Gly Pro Leu Gly Leu Ala Gly Arg Val Val Arg Gly Ser Gly Gly Gly 
    130                 135                 140                 


Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly 
145                 150                 155                 160 


Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu 
                165                 170                 175     


Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe 
            180                 185                 190         


Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys 
        195                 200                 205             


Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu 
    210                 215                 220                 


Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr 
225                 230                 235                 240 


Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg 
                245                 250                 255     


Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr 
            260                 265                 270         


Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser 
        275                 280                 285             


Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe 
    290                 295                 300                 


Gly Ala Phe Leu Val Gly 
305                 310 


<210>  14
<211>  310
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and glycine 
       serine linkers..

<400>  14

Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly 
1               5                   10                  15      


Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu 
            20                  25                  30          


Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe 
        35                  40                  45              


Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys 
    50                  55                  60                  


Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu 
65                  70                  75                  80  


Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr 
                85                  90                  95      


Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg 
            100                 105                 110         


Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr 
        115                 120                 125             


Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser 
    130                 135                 140                 


Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe 
145                 150                 155                 160 


Gly Ala Phe Leu Val Gly Gly Ser Gly Gly Gly Pro Leu Gly Leu Ala 
                165                 170                 175     


Gly Arg Val Val Arg Gly Ser Gly Gly Gly Gln Asp Pro Tyr Val Lys 
            180                 185                 190         


Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val 
        195                 200                 205             


Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu 
    210                 215                 220                 


Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe 
225                 230                 235                 240 


Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val 
                245                 250                 255     


Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys 
            260                 265                 270         


Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp 
        275                 280                 285             


Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala 
    290                 295                 300                 


Glu Leu Ser Pro Ala Ala 
305                 310 


<210>  15
<211>  317
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA, a linker for
       pegylation and glycine-serine linkers..

<400>  15

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Gly Ser Gly Gly 
        115                 120                 125             


Gly Pro Leu Gly Leu Ala Gly Ala Ser Gly Cys Gly Pro Glu Arg Val 
    130                 135                 140                 


Val Arg Gly Ser Gly Gly Gly Glu Arg Gly Pro Gln Arg Val Ala Ala 
145                 150                 155                 160 


His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn 
                165                 170                 175     


Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser 
            180                 185                 190         


Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly 
        195                 200                 205             


Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr 
    210                 215                 220                 


Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys 
225                 230                 235                 240 


Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile 
                245                 250                 255     


Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu 
            260                 265                 270         


Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu 
        275                 280                 285             


Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met 
    290                 295                 300                 


Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu Val Gly 
305                 310                 315         


<210>  16
<211>  338
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA, a linker for
       pegylation and flexible glycine-serine linkers.

<400>  16

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Gly Ser Gly Gly 
        115                 120                 125             


Gly Pro Leu Gly Leu Ala Gly Arg Val Val Arg Ala Ser Gly Cys Gly 
    130                 135                 140                 


Pro Glu Gly Ser Gly Gly Gly Thr Ser Glu Glu Thr Ile Ser Thr Val 
145                 150                 155                 160 


Gln Glu Lys Gln Gln Asn Ile Ser Pro Leu Val Arg Glu Arg Gly Pro 
                165                 170                 175     


Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr 
            180                 185                 190         


Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile 
        195                 200                 205             


Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu 
    210                 215                 220                 


His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr 
225                 230                 235                 240 


Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn 
                245                 250                 255     


Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser 
            260                 265                 270         


Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp 
        275                 280                 285             


Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile 
    290                 295                 300                 


Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu 
305                 310                 315                 320 


His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu 
                325                 330                 335     


Val Gly 
        


<210>  17
<211>  317
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and a linker 
       for pegylation and flexible glycine-serine linkers.

<400>  17

Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly 
1               5                   10                  15      


Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu 
            20                  25                  30          


Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe 
        35                  40                  45              


Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys 
    50                  55                  60                  


Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu 
65                  70                  75                  80  


Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr 
                85                  90                  95      


Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg 
            100                 105                 110         


Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr 
        115                 120                 125             


Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser 
    130                 135                 140                 


Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe 
145                 150                 155                 160 


Gly Ala Phe Leu Val Gly Gly Ser Gly Gly Gly Ala Ser Gly Cys Gly 
                165                 170                 175     


Pro Glu Pro Leu Gly Leu Ala Gly Arg Val Val Arg Gly Ser Gly Gly 
            180                 185                 190         


Gly Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe 
        195                 200                 205             


Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly 
    210                 215                 220                 


Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser 
225                 230                 235                 240 


Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp 
                245                 250                 255     


Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val 
            260                 265                 270         


Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu 
        275                 280                 285             


Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His 
    290                 295                 300                 


Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala 
305                 310                 315         


<210>  18
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and a linker 
       for pegylation and flexible glycine-serine linkers.

<400>  18

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile Asp Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Phe Ser Thr Glu Glu Gln Gln Glu Gly 
        115                 120                 125             


Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly 
    130                 135                 140                 


His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys 
145                 150                 155                 160 


Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val 
                165                 170                 175     


Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile 
            180                 185                 190         


Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe 
        195                 200                 205             


Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr 
    210                 215                 220                 


Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile 
225                 230                 235                 240 


Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg Lys 
                245                 250                 255     


Arg Ser Gln Met Leu Phe Arg Gly Ser Gly Gly Gly Pro Leu Gly Leu 
            260                 265                 270         


Ala Gly Arg Val Val Arg Gly Ser Gly Gly Gly Glu Arg Gly Pro Gln 
        275                 280                 285             


Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr Leu 
    290                 295                 300                 


Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile Asn 
305                 310                 315                 320 


Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu His 
                325                 330                 335     


Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr Ile 
            340                 345                 350         


Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn Thr 
        355                 360                 365             


Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr 
    370                 375                 380                 


Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp Ser 
385                 390                 395                 400 


Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile Phe 
                405                 410                 415     


Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu His 
            420                 425                 430         


Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu Val 
        435                 440                 445             


Gly 
    


<210>  19
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma and a cleavage site
       recognized by metalloprotease MMP and urokinase uPA.

<400>  19

Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly 
1               5                   10                  15      


Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu 
            20                  25                  30          


Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe 
        35                  40                  45              


Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys 
    50                  55                  60                  


Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu 
65                  70                  75                  80  


Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr 
                85                  90                  95      


Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg 
            100                 105                 110         


Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr 
        115                 120                 125             


Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser 
    130                 135                 140                 


Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe 
145                 150                 155                 160 


Gly Ala Phe Leu Val Gly Gly Ser Gly Gly Gly Pro Leu Gly Leu Ala 
                165                 170                 175     


Gly Arg Val Val Arg Gly Ser Gly Gly Gly Gln Asp Pro Tyr Val Lys 
            180                 185                 190         


Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val 
        195                 200                 205             


Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu 
    210                 215                 220                 


Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe 
225                 230                 235                 240 


Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val 
                245                 250                 255     


Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys 
            260                 265                 270         


Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp 
        275                 280                 285             


Leu Asn Val Gln Arg Lys Ala Ile Asp Glu Leu Ile Gln Val Met Ala 
    290                 295                 300                 


Glu Phe Ser Thr Glu Glu Gln Gln Glu Gly Pro Tyr Val Lys Glu Ala 
305                 310                 315                 320 


Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp 
                325                 330                 335     


Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser 
            340                 345                 350         


Asp Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu 
        355                 360                 365             


Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr 
    370                 375                 380                 


Ile Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys 
385                 390                 395                 400 


Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn 
                405                 410                 415     


Val Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu 
            420                 425                 430         


Ser Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe 
        435                 440                 445             


Arg 
    


<210>  20
<211>  456
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and a linker 
       for pegylation and flexible glycine-serine linkers.

<400>  20

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile Asp Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Phe Ser Thr Glu Glu Gln Gln Glu Gly 
        115                 120                 125             


Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly 
    130                 135                 140                 


His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys 
145                 150                 155                 160 


Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val 
                165                 170                 175     


Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile 
            180                 185                 190         


Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe 
        195                 200                 205             


Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr 
    210                 215                 220                 


Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile 
225                 230                 235                 240 


Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg Lys 
                245                 250                 255     


Arg Ser Gln Met Leu Phe Arg Gly Ser Gly Gly Gly Pro Leu Gly Leu 
            260                 265                 270         


Ala Gly Ala Ser Gly Cys Gly Pro Glu Arg Val Val Arg Gly Ser Gly 
        275                 280                 285             


Gly Gly Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr 
    290                 295                 300                 


Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys 
305                 310                 315                 320 


Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His 
                325                 330                 335     


Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His 
            340                 345                 350         


Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln 
        355                 360                 365             


Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr 
    370                 375                 380                 


Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser 
385                 390                 395                 400 


Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser 
                405                 410                 415     


Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe 
            420                 425                 430         


Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser 
        435                 440                 445             


Phe Phe Gly Ala Phe Leu Val Gly 
    450                 455     


<210>  21
<211>  456
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a fragment of human interferon gamma, a cleavage site 
       recognized by metalloprotease MMP and urokinase uPA and a linker 
       for pegylation and flexible glycine-serine linkers.

<400>  21

Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly Thr Arg Gly 
1               5                   10                  15      


Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu 
            20                  25                  30          


Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly His Ser Phe 
        35                  40                  45              


Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile His Glu Lys 
    50                  55                  60                  


Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu 
65                  70                  75                  80  


Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr 
                85                  90                  95      


Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys Ser Ala Arg 
            100                 105                 110         


Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr 
        115                 120                 125             


Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile Phe Val Ser 
    130                 135                 140                 


Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala Ser Phe Phe 
145                 150                 155                 160 


Gly Ala Phe Leu Val Gly Gly Ser Gly Gly Gly Pro Leu Gly Leu Ala 
                165                 170                 175     


Gly Ala Ser Gly Cys Gly Pro Glu Arg Val Val Arg Gly Ser Gly Gly 
            180                 185                 190         


Gly Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe 
        195                 200                 205             


Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly 
    210                 215                 220                 


Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser 
225                 230                 235                 240 


Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp 
                245                 250                 255     


Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val 
            260                 265                 270         


Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu 
        275                 280                 285             


Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile Asp 
    290                 295                 300                 


Glu Leu Ile Gln Val Met Ala Glu Phe Ser Thr Glu Glu Gln Gln Glu 
305                 310                 315                 320 


Gly Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala 
                325                 330                 335     


Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu 
            340                 345                 350         


Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile 
        355                 360                 365             


Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser 
    370                 375                 380                 


Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe 
385                 390                 395                 400 


Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn 
                405                 410                 415     


Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu 
            420                 425                 430         


Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg 
        435                 440                 445             


Lys Arg Ser Gln Met Leu Phe Arg 
    450                 455     


<210>  22
<211>  538
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a single chain pseudodimer of human interferon alpha 2b,
       cleavage site recognized by metalloprotease MMP and urokinase uPA
       and a linker for pegylation.

<400>  22

Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln 
        35                  40                  45              


Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe 
    50                  55                  60                  


Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 
65                  70                  75                  80  


Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu 
                85                  90                  95      


Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 
            100                 105                 110         


Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu 
        115                 120                 125             


Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 
    130                 135                 140                 


Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser 
145                 150                 155                 160 


Leu Arg Ser Lys Glu Gly Gly Gly Gly Ser Pro Leu Gly Leu Ala Gly 
                165                 170                 175     


Arg Val Val Arg Ser Gly Gly Gly Gly Ser Glu Lys Ser Arg Leu Ser 
            180                 185                 190         


Glu Gln Leu Asn Thr Ser Leu Ser Phe Ser Arg Met Ile Glu Ala Arg 
        195                 200                 205             


Val Val Glu Trp Ala Cys Pro Ser Tyr Lys Lys Glu Lys Leu Tyr Leu 
    210                 215                 220                 


Thr Ile Arg Gln Phe Tyr Phe Arg Val Ala Leu Ile Ser Asp Glu Lys 
225                 230                 235                 240 


Met Leu Pro Thr Glu Thr Val Gly Val Gly Gln Ile Val Cys Ala Glu 
                245                 250                 255     


Leu Asp Asn Leu Gln Gln Tyr Leu Glu Thr Tyr Phe Lys Asp Leu Leu 
            260                 265                 270         


Thr Glu Asp Trp Ala Ala Ser Ser Asp Lys Thr Ser Phe Leu Asn Phe 
        275                 280                 285             


Ile Gln Gln Ile Met Glu His Leu Val Pro Ile Thr Glu Ala Lys Gln 
    290                 295                 300                 


Phe Gln Asn Gly Phe Glu Glu Gln Pro Phe Gly Phe Asp His Arg Asp 
305                 310                 315                 320 


Lys Leu Cys Ser Phe Leu Ser Ile Arg Arg Met Gln Ala Leu Leu Met 
                325                 330                 335     


Leu Thr Arg Arg Ser Gly Leu Ser His Thr Gln Pro Leu Asp Cys Pro 
            340                 345                 350         


Leu Gly Leu Ala Gly Arg Val Val Arg Ala Ser Gly Cys Gly Pro Glu 
        355                 360                 365             


Pro Leu Gly Leu Ala Gly Arg Val Val Arg Val Ala Ala His Ile Thr 
    370                 375                 380                 


Gly Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn 
385                 390                 395                 400 


Glu Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser 
                405                 410                 415     


Gly His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val 
            420                 425                 430         


Ile His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg 
        435                 440                 445             


Phe Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val 
    450                 455                 460                 


Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met 
465                 470                 475                 480 


Lys Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu 
                485                 490                 495     


Tyr Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg 
            500                 505                 510         


Ile Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu 
        515                 520                 525             


Ala Ser Phe Phe Gly Ala Phe Leu Val Gly 
    530                 535             


<210>  23
<211>  384
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized, a fusion protein comprising: a fragment of TRAIL 
       protein, a consensus sequence of human interferon alpha, cleavage
       site recognized by metalloprotease MMP and urokinase uPA and, 
       linker for pegylation and flexible glycine-serine linker.

<400>  23

Ser Asp Leu Pro Gln Thr His Ser Leu Gly Asn Arg Arg Ala Leu Ile 
1               5                   10                  15      


Leu Leu Ala Gln Met Arg Arg Ile Ser Pro Phe Ser Cys Leu Lys Asp 
            20                  25                  30          


Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Asp Gly Asn Gln Phe 
        35                  40                  45              


Gln Lys Ala Gln Ala Ile Ser Val Leu His Glu Met Ile Gln Gln Thr 
    50                  55                  60                  


Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Ser 
65                  70                  75                  80  


Leu Leu Glu Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu 
                85                  90                  95      


Glu Ala Cys Val Ile Gln Glu Val Gly Val Glu Glu Thr Pro Leu Met 
            100                 105                 110         


Asn Val Asp Ser Ile Leu Ala Val Lys Lys Tyr Phe Gln Arg Ile Thr 
        115                 120                 125             


Leu Tyr Leu Thr Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val 
    130                 135                 140                 


Arg Ala Glu Ile Met Arg Ser Phe Ser Ile Ser Thr Asn Leu Gln Glu 
145                 150                 155                 160 


Arg Leu Arg Arg Lys Glu Gly Gly Ser Gly Pro Leu Gly Leu Ala Gly 
                165                 170                 175     


Arg Val Val Arg Ala Ser Gly Cys Gly Pro Glu Pro Leu Gly Leu Ala 
            180                 185                 190         


Gly Arg Val Val Arg Thr Ser Glu Glu Thr Ile Ser Thr Val Gln Glu 
        195                 200                 205             


Lys Gln Gln Asn Ile Ser Pro Leu Val Arg Glu Arg Gly Pro Gln Arg 
    210                 215                 220                 


Val Ala Ala His Ile Thr Gly Thr Arg Gly Arg Ser Asn Thr Leu Ser 
225                 230                 235                 240 


Ser Pro Asn Ser Lys Asn Glu Lys Ala Leu Gly Arg Lys Ile Asn Ser 
                245                 250                 255     


Trp Glu Ser Ser Arg Ser Gly His Ser Phe Leu Ser Asn Leu His Leu 
            260                 265                 270         


Arg Asn Gly Glu Leu Val Ile His Glu Lys Gly Phe Tyr Tyr Ile Tyr 
        275                 280                 285             


Ser Gln Thr Tyr Phe Arg Phe Gln Glu Glu Ile Lys Glu Asn Thr Lys 
    290                 295                 300                 


Asn Asp Lys Gln Met Val Gln Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro 
305                 310                 315                 320 


Asp Pro Ile Leu Leu Met Lys Ser Ala Arg Asn Ser Cys Trp Ser Lys 
                325                 330                 335     


Asp Ala Glu Tyr Gly Leu Tyr Ser Ile Tyr Gln Gly Gly Ile Phe Glu 
            340                 345                 350         


Leu Lys Glu Asn Asp Arg Ile Phe Val Ser Val Thr Asn Glu His Leu 
        355                 360                 365             


Ile Asp Met Asp His Glu Ala Ser Phe Phe Gly Ala Phe Leu Val Gly 
    370                 375                 380                 


