                         SEQUENCE LISTING

<110>  Washington University
       Janetka, James W
       Han, Zhenfu
       Harris, Peter
       Karmakar, Partha
 
<120>  INHIBITORS OF GROWTH FACTOR ACTIVATION ENZYMES

<130>  WSTL 14793.WO

<150>  US62/220998
<151>  2015-09-19

<150>  US62/130117
<151>  2015-03-09

<160>  25    

<170>  PatentIn version 3.5

<210>  1
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  1

Lys Gln Leu Arg 
1               


<210>  2
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  2

Lys His Leu Arg 
1               


<210>  3
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  3

Trp Gln Leu Arg 
1               


<210>  4
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  4

Lys Phe Leu Arg 
1               


<210>  5
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  5

Lys Phe Leu Arg 
1               


<210>  6
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  6

Arg Gln Leu Arg 
1               


<210>  7
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  7

Ser Gln Leu Arg 
1               


<210>  8
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  8

Lys Arg Leu Arg 
1               


<210>  9
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  9

Trp Arg Leu Arg 
1               


<210>  10
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  10

Ser Lys Leu Arg 
1               


<210>  11
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  11

Ser His Leu Arg 
1               


<210>  12
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  12

Trp Lys Leu Arg 
1               


<210>  13
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  13

Ser Lys Phe Arg 
1               


<210>  14
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  14

Asn Lys Leu Arg 
1               


<210>  15
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  15

Ser Arg Leu Arg 
1               


<210>  16
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  16

Thr Lys Leu Arg 
1               


<210>  17
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  17

Ser Trp Leu Arg 
1               


<210>  18
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  18

Arg Lys Leu Arg 
1               


<210>  19
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  19

Phe Leu Phe Arg 
1               


<210>  20
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  20

Trp Leu Phe Arg 
1               


<210>  21
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  21
gtccaactgt caccggatct c                                                 21


<210>  22
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic

<400>  22
ccgccgaaca ccgagggagg actttcgaac ggcgg                                  35


<210>  23
<211>  655
<212>  PRT
<213>  Homo sapiens

<400>  23

Met Gly Arg Trp Ala Trp Val Pro Ser Pro Trp Pro Pro Pro Gly Leu 
1               5                   10                  15      


Gly Pro Phe Leu Leu Leu Leu Leu Leu Leu Leu Leu Leu Pro Arg Gly 
            20                  25                  30          


Phe Gln Pro Gln Pro Gly Gly Asn Arg Thr Glu Ser Pro Glu Pro Asn 
        35                  40                  45              


Ala Thr Ala Thr Pro Ala Ile Pro Thr Ile Leu Val Thr Ser Val Thr 
    50                  55                  60                  


Ser Glu Thr Pro Ala Thr Ser Ala Pro Glu Ala Glu Gly Pro Gln Ser 
65                  70                  75                  80  


Gly Gly Leu Pro Pro Pro Pro Arg Ala Val Pro Ser Ser Ser Ser Pro 
                85                  90                  95      


Gln Ala Gln Ala Leu Thr Glu Asp Gly Arg Pro Cys Arg Phe Pro Phe 
            100                 105                 110         


Arg Tyr Gly Gly Arg Met Leu His Ala Cys Thr Ser Glu Gly Ser Ala 
        115                 120                 125             


His Arg Lys Trp Cys Ala Thr Thr His Asn Tyr Asp Arg Asp Arg Ala 
    130                 135                 140                 


Trp Gly Tyr Cys Val Glu Ala Thr Pro Pro Pro Gly Gly Pro Ala Ala 
145                 150                 155                 160 


Leu Asp Pro Cys Ala Ser Gly Pro Cys Leu Asn Gly Gly Ser Cys Ser 
                165                 170                 175     


Asn Thr Gln Asp Pro Gln Ser Tyr His Cys Ser Cys Pro Arg Ala Phe 
            180                 185                 190         


Thr Gly Lys Asp Cys Gly Thr Glu Lys Cys Phe Asp Glu Thr Arg Tyr 
        195                 200                 205             


Glu Tyr Leu Glu Gly Gly Asp Arg Trp Ala Arg Val Arg Gln Gly His 
    210                 215                 220                 


Val Glu Gln Cys Glu Cys Phe Gly Gly Arg Thr Trp Cys Glu Gly Thr 
225                 230                 235                 240 


Arg His Thr Ala Cys Leu Ser Ser Pro Cys Leu Asn Gly Gly Thr Cys 
                245                 250                 255     


His Leu Ile Val Ala Thr Gly Thr Thr Val Cys Ala Cys Pro Pro Gly 
            260                 265                 270         


Phe Ala Gly Arg Leu Cys Asn Ile Glu Pro Asp Glu Arg Cys Phe Leu 
        275                 280                 285             


Gly Asn Gly Thr Gly Tyr Arg Gly Val Ala Ser Thr Ser Ala Ser Gly 
    290                 295                 300                 


Leu Ser Cys Leu Ala Trp Asn Ser Asp Leu Leu Tyr Gln Glu Leu His 
305                 310                 315                 320 


Val Asp Ser Val Gly Ala Ala Ala Leu Leu Gly Leu Gly Pro His Ala 
                325                 330                 335     


Tyr Cys Arg Asn Pro Asp Asn Asp Glu Arg Pro Trp Cys Tyr Val Val 
            340                 345                 350         


Lys Asp Ser Ala Leu Ser Trp Glu Tyr Cys Arg Leu Glu Ala Cys Glu 
        355                 360                 365             


Ser Leu Thr Arg Val Gln Leu Ser Pro Asp Leu Leu Ala Thr Leu Pro 
    370                 375                 380                 


Glu Pro Ala Ser Pro Gly Arg Gln Ala Cys Gly Arg Arg His Lys Lys 
385                 390                 395                 400 


Arg Thr Phe Leu Arg Pro Arg Ile Ile Gly Gly Ser Ser Ser Leu Pro 
                405                 410                 415     


Gly Ser His Pro Trp Leu Ala Ala Ile Tyr Ile Gly Asp Ser Phe Cys 
            420                 425                 430         


Ala Gly Ser Leu Val His Thr Cys Trp Val Val Ser Ala Ala His Cys 
        435                 440                 445             


Phe Ser His Ser Pro Pro Arg Asp Ser Val Ser Val Val Leu Gly Gln 
    450                 455                 460                 


His Phe Phe Asn Arg Thr Thr Asp Val Thr Gln Thr Phe Gly Ile Glu 
465                 470                 475                 480 


Lys Tyr Ile Pro Tyr Thr Leu Tyr Ser Val Phe Asn Pro Ser Asp His 
                485                 490                 495     


Asp Leu Val Leu Ile Arg Leu Lys Lys Lys Gly Asp Arg Cys Ala Thr 
            500                 505                 510         


Arg Ser Gln Phe Val Gln Pro Ile Cys Leu Pro Glu Pro Gly Ser Thr 
        515                 520                 525             


Phe Pro Ala Gly His Lys Cys Gln Ile Ala Gly Trp Gly His Leu Asp 
    530                 535                 540                 


Glu Asn Val Ser Gly Tyr Ser Ser Ser Leu Arg Glu Ala Leu Val Pro 
545                 550                 555                 560 


Leu Val Ala Asp His Lys Cys Ser Ser Pro Glu Val Tyr Gly Ala Asp 
                565                 570                 575     


Ile Ser Pro Asn Met Leu Cys Ala Gly Tyr Phe Asp Cys Lys Ser Asp 
            580                 585                 590         


Ala Cys Gln Gly Asp Ser Gly Gly Pro Leu Ala Cys Glu Lys Asn Gly 
        595                 600                 605             


Val Ala Tyr Leu Tyr Gly Ile Ile Ser Trp Gly Asp Gly Cys Gly Arg 
    610                 615                 620                 


Leu His Lys Pro Gly Val Tyr Thr Arg Val Ala Asn Tyr Val Asp Trp 
625                 630                 635                 640 


Ile Asn Asp Arg Ile Arg Pro Pro Arg Arg Leu Val Ala Pro Ser 
                645                 650                 655 


<210>  24
<211>  855
<212>  PRT
<213>  Homo sapiens

<400>  24

Met Gly Ser Asp Arg Ala Arg Lys Gly Gly Gly Gly Pro Lys Asp Phe 
1               5                   10                  15      


Gly Ala Gly Leu Lys Tyr Asn Ser Arg His Glu Lys Val Asn Gly Leu 
            20                  25                  30          


Glu Glu Gly Val Glu Phe Leu Pro Val Asn Asn Val Lys Lys Val Glu 
        35                  40                  45              


Lys His Gly Pro Gly Arg Trp Val Val Leu Ala Ala Val Leu Ile Gly 
    50                  55                  60                  


Leu Leu Leu Val Leu Leu Gly Ile Gly Phe Leu Val Trp His Leu Gln 
65                  70                  75                  80  


Tyr Arg Asp Val Arg Val Gln Lys Val Phe Asn Gly Tyr Met Arg Ile 
                85                  90                  95      


Thr Asn Glu Asn Phe Val Asp Ala Tyr Glu Asn Ser Asn Ser Thr Glu 
            100                 105                 110         


Phe Val Ser Leu Ala Ser Lys Val Lys Asp Ala Leu Lys Leu Leu Tyr 
        115                 120                 125             


Ser Gly Val Pro Phe Leu Gly Pro Tyr His Lys Glu Ser Ala Val Thr 
    130                 135                 140                 


Ala Phe Ser Glu Gly Ser Val Ile Ala Tyr Tyr Trp Ser Glu Phe Ser 
145                 150                 155                 160 


Ile Pro Gln His Leu Val Glu Glu Ala Glu Arg Val Met Ala Glu Glu 
                165                 170                 175     


Arg Val Val Met Leu Pro Pro Arg Ala Arg Ser Leu Lys Ser Phe Val 
            180                 185                 190         


Val Thr Ser Val Val Ala Phe Pro Thr Asp Ser Lys Thr Val Gln Arg 
        195                 200                 205             


Thr Gln Asp Asn Ser Cys Ser Phe Gly Leu His Ala Arg Gly Val Glu 
    210                 215                 220                 


Leu Met Arg Phe Thr Thr Pro Gly Phe Pro Asp Ser Pro Tyr Pro Ala 
225                 230                 235                 240 


His Ala Arg Cys Gln Trp Ala Leu Arg Gly Asp Ala Asp Ser Val Leu 
                245                 250                 255     


Ser Leu Thr Phe Arg Ser Phe Asp Leu Ala Ser Cys Asp Glu Arg Gly 
            260                 265                 270         


Ser Asp Leu Val Thr Val Tyr Asn Thr Leu Ser Pro Met Glu Pro His 
        275                 280                 285             


Ala Leu Val Gln Leu Cys Gly Thr Tyr Pro Pro Ser Tyr Asn Leu Thr 
    290                 295                 300                 


Phe His Ser Ser Gln Asn Val Leu Leu Ile Thr Leu Ile Thr Asn Thr 
305                 310                 315                 320 


Glu Arg Arg His Pro Gly Phe Glu Ala Thr Phe Phe Gln Leu Pro Arg 
                325                 330                 335     


Met Ser Ser Cys Gly Gly Arg Leu Arg Lys Ala Gln Gly Thr Phe Asn 
            340                 345                 350         


Ser Pro Tyr Tyr Pro Gly His Tyr Pro Pro Asn Ile Asp Cys Thr Trp 
        355                 360                 365             


Asn Ile Glu Val Pro Asn Asn Gln His Val Lys Val Arg Phe Lys Phe 
    370                 375                 380                 


Phe Tyr Leu Leu Glu Pro Gly Val Pro Ala Gly Thr Cys Pro Lys Asp 
385                 390                 395                 400 


Tyr Val Glu Ile Asn Gly Glu Lys Tyr Cys Gly Glu Arg Ser Gln Phe 
                405                 410                 415     


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


Gln Ser Tyr Thr Asp Thr Gly Phe Leu Ala Glu Tyr Leu Ser Tyr Asp 
        435                 440                 445             


Ser Ser Asp Pro Cys Pro Gly Gln Phe Thr Cys Arg Thr Gly Arg Cys 
    450                 455                 460                 


Ile Arg Lys Glu Leu Arg Cys Asp Gly Trp Ala Asp Cys Thr Asp His 
465                 470                 475                 480 


Ser Asp Glu Leu Asn Cys Ser Cys Asp Ala Gly His Gln Phe Thr Cys 
                485                 490                 495     


Lys Asn Lys Phe Cys Lys Pro Leu Phe Trp Val Cys Asp Ser Val Asn 
            500                 505                 510         


Asp Cys Gly Asp Asn Ser Asp Glu Gln Gly Cys Ser Cys Pro Ala Gln 
        515                 520                 525             


Thr Phe Arg Cys Ser Asn Gly Lys Cys Leu Ser Lys Ser Gln Gln Cys 
    530                 535                 540                 


Asn Gly Lys Asp Asp Cys Gly Asp Gly Ser Asp Glu Ala Ser Cys Pro 
545                 550                 555                 560 


Lys Val Asn Val Val Thr Cys Thr Lys His Thr Tyr Arg Cys Leu Asn 
                565                 570                 575     


Gly Leu Cys Leu Ser Lys Gly Asn Pro Glu Cys Asp Gly Lys Glu Asp 
            580                 585                 590         


Cys Ser Asp Gly Ser Asp Glu Lys Asp Cys Asp Cys Gly Leu Arg Ser 
        595                 600                 605             


Phe Thr Arg Gln Ala Arg Val Val Gly Gly Thr Asp Ala Asp Glu Gly 
    610                 615                 620                 


Glu Trp Pro Trp Gln Val Ser Leu His Ala Leu Gly Gln Gly His Ile 
625                 630                 635                 640 


Cys Gly Ala Ser Leu Ile Ser Pro Asn Trp Leu Val Ser Ala Ala His 
                645                 650                 655     


Cys Tyr Ile Asp Asp Arg Gly Phe Arg Tyr Ser Asp Pro Thr Gln Trp 
            660                 665                 670         


Thr Ala Phe Leu Gly Leu His Asp Gln Ser Gln Arg Ser Ala Pro Gly 
        675                 680                 685             


Val Gln Glu Arg Arg Leu Lys Arg Ile Ile Ser His Pro Phe Phe Asn 
    690                 695                 700                 


Asp Phe Thr Phe Asp Tyr Asp Ile Ala Leu Leu Glu Leu Glu Lys Pro 
705                 710                 715                 720 


Ala Glu Tyr Ser Ser Met Val Arg Pro Ile Cys Leu Pro Asp Ala Ser 
                725                 730                 735     


His Val Phe Pro Ala Gly Lys Ala Ile Trp Val Thr Gly Trp Gly His 
            740                 745                 750         


Thr Gln Tyr Gly Gly Thr Gly Ala Leu Ile Leu Gln Lys Gly Glu Ile 
        755                 760                 765             


Arg Val Ile Asn Gln Thr Thr Cys Glu Asn Leu Leu Pro Gln Gln Ile 
    770                 775                 780                 


Thr Pro Arg Met Met Cys Val Gly Phe Leu Ser Gly Gly Val Asp Ser 
785                 790                 795                 800 


Cys Gln Gly Asp Ser Gly Gly Pro Leu Ser Ser Val Glu Ala Asp Gly 
                805                 810                 815     


Arg Ile Phe Gln Ala Gly Val Val Ser Trp Gly Asp Gly Cys Ala Gln 
            820                 825                 830         


Arg Asn Lys Pro Gly Val Tyr Thr Arg Leu Pro Leu Phe Arg Asp Trp 
        835                 840                 845             


Ile Lys Glu Asn Thr Gly Val 
    850                 855 


<210>  25
<211>  417
<212>  PRT
<213>  Homo sapiens

<400>  25

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


Lys Val Ala Ala Leu Thr Ala Gly Thr Leu Leu Leu Leu Thr Ala Ile 
            20                  25                  30          


Gly Ala Ala Ser Trp Ala Ile Val Ala Val Leu Leu Arg Ser Asp Gln 
        35                  40                  45              


Glu Pro Leu Tyr Pro Val Gln Val Ser Ser Ala Asp Ala Arg Leu Met 
    50                  55                  60                  


Val Phe Asp Lys Thr Glu Gly Thr Trp Arg Leu Leu Cys Ser Ser Arg 
65                  70                  75                  80  


Ser Asn Ala Arg Val Ala Gly Leu Ser Cys Glu Glu Met Gly Phe Leu 
                85                  90                  95      


Arg Ala Leu Thr His Ser Glu Leu Asp Val Arg Thr Ala Gly Ala Asn 
            100                 105                 110         


Gly Thr Ser Gly Phe Phe Cys Val Asp Glu Gly Arg Leu Pro His Thr 
        115                 120                 125             


Gln Arg Leu Leu Glu Val Ile Ser Val Cys Asp Cys Pro Arg Gly Arg 
    130                 135                 140                 


Phe Leu Ala Ala Ile Cys Gln Asp Cys Gly Arg Arg Lys Leu Pro Val 
145                 150                 155                 160 


Asp Arg Ile Val Gly Gly Arg Asp Thr Ser Leu Gly Arg Trp Pro Trp 
                165                 170                 175     


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


Leu Ser Gly Asp Trp Val Leu Thr Ala Ala His Cys Phe Pro Glu Arg 
        195                 200                 205             


Asn Arg Val Leu Ser Arg Trp Arg Val Phe Ala Gly Ala Val Ala Gln 
    210                 215                 220                 


Ala Ser Pro His Gly Leu Gln Leu Gly Val Gln Ala Val Val Tyr His 
225                 230                 235                 240 


Gly Gly Tyr Leu Pro Phe Arg Asp Pro Asn Ser Glu Glu Asn Ser Asn 
                245                 250                 255     


Asp Ile Ala Leu Val His Leu Ser Ser Pro Leu Pro Leu Thr Glu Tyr 
            260                 265                 270         


Ile Gln Pro Val Cys Leu Pro Ala Ala Gly Gln Ala Leu Val Asp Gly 
        275                 280                 285             


Lys Ile Cys Thr Val Thr Gly Trp Gly Asn Thr Gln Tyr Tyr Gly Gln 
    290                 295                 300                 


Gln Ala Gly Val Leu Gln Glu Ala Arg Val Pro Ile Ile Ser Asn Asp 
305                 310                 315                 320 


Val Cys Asn Gly Ala Asp Phe Tyr Gly Asn Gln Ile Lys Pro Lys Met 
                325                 330                 335     


Phe Cys Ala Gly Tyr Pro Glu Gly Gly Ile Asp Ala Cys Gln Gly Asp 
            340                 345                 350         


Ser Gly Gly Pro Phe Val Cys Glu Asp Ser Ile Ser Arg Thr Pro Arg 
        355                 360                 365             


Trp Arg Leu Cys Gly Ile Val Ser Trp Gly Thr Gly Cys Ala Leu Ala 
    370                 375                 380                 


Gln Lys Pro Gly Val Tyr Thr Lys Val Ser Asp Phe Arg Glu Trp Ile 
385                 390                 395                 400 


Phe Gln Ala Ile Lys Thr His Ser Glu Ala Ser Gly Met Val Thr Gln 
                405                 410                 415     


Leu 
    


