                         SEQUENCE LISTING

<110>  The Regents of the University of California
       The University of Tokyo
       Shokat, Kevan M.
       Suga, Hiroaki
       Zhang, Ziyang
       Gao, Rong
 
<120>  Ras Inhibitors and Uses Thereof

<130>  048536-684001WO

<150>  US 63/014,596
<151>  2020-04-23

<160>  8     

<170>  PatentIn version 3.5

<210>  1
<211>  189
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  1

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys 
1               5                   10                  15      


Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr 
            20                  25                  30          


Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly 
        35                  40                  45              


Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr 
    50                  55                  60                  


Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys 
65                  70                  75                  80  


Val Phe Ala Ile Asn Asn Thr Lys Ser Phe Glu Asp Ile His His Tyr 
                85                  90                  95      


Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Glu Asp Val Pro Met Val 
            100                 105                 110         


Leu Val Gly Asn Lys Cys Asp Leu Pro Ser Arg Thr Val Asp Thr Lys 
        115                 120                 125             


Gln Ala Gln Asp Leu Ala Arg Ser Tyr Gly Ile Pro Phe Ile Glu Thr 
    130                 135                 140                 


Ser Ala Lys Thr Arg Gln Arg Val Glu Asp Ala Phe Tyr Thr Leu Val 
145                 150                 155                 160 


Arg Glu Ile Arg Gln Tyr Arg Leu Lys Lys Ile Ser Lys Glu Glu Lys 
                165                 170                 175     


Thr Pro Gly Cys Val Lys Ile Lys Lys Cys Ile Ile Met 
            180                 185                 


<210>  2
<211>  189
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  2

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys 
1               5                   10                  15      


Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr 
            20                  25                  30          


Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly 
        35                  40                  45              


Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr 
    50                  55                  60                  


Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys 
65                  70                  75                  80  


Val Phe Ala Ile Asn Asn Thr Lys Ser Phe Glu Asp Ile His Gln Tyr 
                85                  90                  95      


Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Asp Asp Val Pro Met Val 
            100                 105                 110         


Leu Val Gly Asn Lys Cys Asp Leu Ala Ala Arg Thr Val Glu Ser Arg 
        115                 120                 125             


Gln Ala Gln Asp Leu Ala Arg Ser Tyr Gly Ile Pro Tyr Ile Glu Thr 
    130                 135                 140                 


Ser Ala Lys Thr Arg Gln Gly Val Glu Asp Ala Phe Tyr Thr Leu Val 
145                 150                 155                 160 


Arg Glu Ile Arg Gln His Lys Leu Arg Lys Leu Asn Pro Pro Asp Glu 
                165                 170                 175     


Ser Gly Pro Gly Cys Met Ser Cys Lys Cys Val Leu Ser 
            180                 185                 


<210>  3
<211>  189
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  3

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys 
1               5                   10                  15      


Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr 
            20                  25                  30          


Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly 
        35                  40                  45              


Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr 
    50                  55                  60                  


Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys 
65                  70                  75                  80  


Val Phe Ala Ile Asn Asn Ser Lys Ser Phe Ala Asp Ile Asn Leu Tyr 
                85                  90                  95      


Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Asp Asp Val Pro Met Val 
            100                 105                 110         


Leu Val Gly Asn Lys Cys Asp Leu Pro Thr Arg Thr Val Asp Thr Lys 
        115                 120                 125             


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


Ser Ala Lys Thr Arg Gln Gly Val Glu Asp Ala Phe Tyr Thr Leu Val 
145                 150                 155                 160 


Arg Glu Ile Arg Gln Tyr Arg Met Lys Lys Leu Asn Ser Ser Asp Asp 
                165                 170                 175     


Gly Thr Gln Gly Cys Met Gly Leu Pro Cys Val Val Met 
            180                 185                 


<210>  4
<211>  187
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  4

Met His His His His His His Ser Ser Gly Arg Glu Asn Leu Tyr Phe 
1               5                   10                  15      


Gln Gly Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Asp Gly Val 
            20                  25                  30          


Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp 
        35                  40                  45              


Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile 
    50                  55                  60                  


Asp Gly Glu Thr Ser Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu 
65                  70                  75                  80  


Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe 
                85                  90                  95      


Leu Leu Val Phe Ala Ile Asn Asn Thr Lys Ser Phe Glu Asp Ile His 
            100                 105                 110         


His Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Glu Asp Val Pro 
        115                 120                 125             


Met Val Leu Val Gly Asn Lys Ser Asp Leu Pro Ser Arg Thr Val Asp 
    130                 135                 140                 


Thr Lys Gln Ala Gln Asp Leu Ala Arg Ser Tyr Gly Ile Pro Phe Ile 
145                 150                 155                 160 


Glu Thr Ser Ala Lys Thr Arg Gln Gly Val Asp Asp Ala Phe Tyr Thr 
                165                 170                 175     


Leu Val Arg Glu Ile Arg Lys His Lys Glu Lys 
            180                 185         


<210>  5
<211>  208
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  5

Met Gly Ser Ser His His His His His His Ser Gly Met Ser Gly Leu 
1               5                   10                  15      


Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu Ser Ser Gly 
            20                  25                  30          


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


Gly Ala Asp Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln 
    50                  55                  60                  


Asn His Phe Val Asp Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg 
65                  70                  75                  80  


Lys Gln Val Val Ile Asp Gly Glu Thr Cys Leu Leu Asp Ile Leu Asp 
                85                  90                  95      


Thr Ala Gly Gln Glu Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg 
            100                 105                 110         


Thr Gly Glu Gly Phe Leu Cys Val Phe Ala Ile Asn Asn Thr Lys Ser 
        115                 120                 125             


Phe Glu Asp Ile His His Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp 
    130                 135                 140                 


Ser Glu Asp Val Pro Met Val Leu Val Gly Asn Lys Cys Asp Leu Pro 
145                 150                 155                 160 


Ser Arg Thr Val Asp Thr Lys Gln Ala Gln Asp Leu Ala Arg Ser Tyr 
                165                 170                 175     


Gly Ile Pro Phe Ile Glu Thr Ser Ala Lys Thr Arg Gln Gly Val Asp 
            180                 185                 190         


Asp Ala Phe Tyr Thr Leu Val Arg Glu Ile Arg Lys His Lys Glu Lys 
        195                 200                 205             


<210>  6
<211>  208
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  6

Met Gly Ser Ser His His His His His His Ser Gly Met Ser Gly Leu 
1               5                   10                  15      


Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu Ser Ser Gly 
            20                  25                  30          


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


Gly Ala Gly Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln 
    50                  55                  60                  


Asn His Phe Val Asp Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg 
65                  70                  75                  80  


Lys Gln Val Val Ile Asp Gly Glu Thr Cys Leu Leu Asp Ile Leu Asp 
                85                  90                  95      


Thr Ala Gly Gln Glu Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg 
            100                 105                 110         


Thr Gly Glu Gly Phe Leu Cys Val Phe Ala Ile Asn Asn Thr Lys Ser 
        115                 120                 125             


Phe Glu Asp Ile His His Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp 
    130                 135                 140                 


Ser Glu Asp Val Pro Met Val Leu Val Gly Asn Lys Cys Asp Leu Pro 
145                 150                 155                 160 


Ser Arg Thr Val Asp Thr Lys Gln Ala Gln Asp Leu Ala Arg Ser Tyr 
                165                 170                 175     


Gly Ile Pro Phe Ile Glu Thr Ser Ala Lys Thr Arg Gln Gly Val Asp 
            180                 185                 190         


Asp Ala Phe Tyr Thr Leu Val Arg Glu Ile Arg Lys His Lys Glu Lys 
        195                 200                 205             


<210>  7
<211>  384
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  7

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys 
    50                  55                  60                  


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


Gly Ser Pro Ile His Ile Met Glu His Ile Gln Gly Ala Trp Lys Thr 
225                 230                 235                 240 


Ile Ser Asn Gly Phe Gly Phe Lys Asp Ala Val Phe Asp Gly Ser Ser 
                245                 250                 255     


Cys Ile Ser Pro Thr Ile Val Gln Gln Phe Gly Tyr Gln Arg Arg Ala 
            260                 265                 270         


Ser Asp Asp Gly Lys Leu Thr Asp Pro Ser Lys Thr Ser Asn Thr Ile 
        275                 280                 285             


Arg Val Phe Leu Pro Asn Lys Gln Arg Thr Val Val Asn Val Arg Asn 
    290                 295                 300                 


Gly Met Ser Leu His Asp Cys Leu Met Lys Ala Leu Lys Val Arg Gly 
305                 310                 315                 320 


Leu Gln Pro Glu Cys Cys Ala Val Phe Arg Leu Leu His Glu His Lys 
                325                 330                 335     


Gly Lys Lys Ala Arg Leu Asp Trp Asn Thr Asp Ala Ala Ser Leu Ile 
            340                 345                 350         


Gly Glu Glu Leu Gln Val Asp Phe Leu Asp His Val Pro Leu Thr Thr 
        355                 360                 365             


His Asn Phe Ala Arg Lys Thr Phe Leu Lys Leu Gly Ile His Arg Asp 
    370                 375                 380                 


<210>  8
<211>  1002
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic polypeptide

<400>  8

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys 
    50                  55                  60                  


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Glu Val Leu 
    210                 215                 220                 


Phe Gln Gly Pro Leu Gly Ser Pro Asn Ser Arg Val Asp Ala Ala Leu 
225                 230                 235                 240 


Ser Gly Gly Gly Gly Gly Gly Ala Glu Pro Gly Gln Ala Leu Phe Asn 
                245                 250                 255     


Gly Asp Met Glu Pro Glu Ala Gly Ala Gly Ala Gly Ala Ala Ala Ser 
            260                 265                 270         


Ser Ala Ala Asp Pro Ala Ile Pro Glu Glu Val Trp Asn Ile Lys Gln 
        275                 280                 285             


Met Ile Lys Leu Thr Gln Glu His Ile Glu Ala Leu Leu Asp Lys Phe 
    290                 295                 300                 


Gly Gly Glu His Asn Pro Pro Ser Ile Tyr Leu Glu Ala Tyr Glu Glu 
305                 310                 315                 320 


Tyr Thr Ser Lys Leu Asp Ala Leu Gln Gln Arg Glu Gln Gln Leu Leu 
                325                 330                 335     


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


Met Asp Thr Val Thr Ser Ser Ser Ser Ser Ser Leu Ser Val Leu Pro 
        355                 360                 365             


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


Pro Lys Ser Pro Gln Lys Pro Ile Val Arg Val Phe Leu Pro Asn Lys 
385                 390                 395                 400 


Gln Arg Thr Val Val Pro Ala Arg Cys Gly Val Thr Val Arg Asp Ser 
                405                 410                 415     


Leu Lys Lys Ala Leu Met Met Arg Gly Leu Ile Pro Glu Cys Cys Ala 
            420                 425                 430         


Val Tyr Arg Ile Gln Asp Gly Glu Lys Lys Pro Ile Gly Trp Asp Thr 
        435                 440                 445             


Asp Ile Ser Trp Leu Thr Gly Glu Glu Leu His Val Glu Val Leu Glu 
    450                 455                 460                 


Asn Val Pro Leu Thr Thr His Asn Phe Val Arg Lys Thr Phe Phe Thr 
465                 470                 475                 480 


Leu Ala Phe Cys Asp Phe Cys Arg Lys Leu Leu Phe Gln Gly Phe Arg 
                485                 490                 495     


Cys Gln Thr Cys Gly Tyr Lys Phe His Gln Arg Cys Ser Thr Glu Val 
            500                 505                 510         


Pro Leu Met Cys Val Asn Tyr Asp Gln Leu Asp Leu Leu Phe Val Ser 
        515                 520                 525             


Lys Phe Phe Glu His His Pro Ile Pro Gln Glu Glu Ala Ser Leu Ala 
    530                 535                 540                 


Glu Thr Ala Leu Thr Ser Gly Ser Ser Pro Ser Ala Pro Ala Ser Asp 
545                 550                 555                 560 


Ser Ile Gly Pro Gln Ile Leu Thr Ser Pro Ser Pro Ser Lys Ser Ile 
                565                 570                 575     


Pro Ile Pro Gln Pro Phe Arg Pro Ala Asp Glu Asp His Arg Asn Gln 
            580                 585                 590         


Phe Gly Gln Arg Asp Arg Ser Ser Ser Ala Pro Asn Val His Ile Asn 
        595                 600                 605             


Thr Ile Glu Pro Val Asn Ile Asp Asp Leu Ile Arg Asp Gln Gly Phe 
    610                 615                 620                 


Arg Gly Asp Gly Gly Ser Thr Thr Gly Leu Ser Ala Thr Pro Pro Ala 
625                 630                 635                 640 


Ser Leu Pro Gly Ser Leu Thr Asn Val Lys Ala Leu Gln Lys Ser Pro 
                645                 650                 655     


Gly Pro Gln Arg Glu Arg Lys Ser Ser Ser Ser Ser Glu Asp Arg Asn 
            660                 665                 670         


Arg Met Lys Thr Leu Gly Arg Arg Asp Ser Ser Asp Asp Trp Glu Ile 
        675                 680                 685             


Pro Asp Gly Gln Ile Thr Val Gly Gln Arg Ile Gly Ser Gly Ser Phe 
    690                 695                 700                 


Gly Thr Val Tyr Lys Gly Lys Trp His Gly Asp Val Ala Val Lys Met 
705                 710                 715                 720 


Leu Asn Val Thr Ala Pro Thr Pro Gln Gln Leu Gln Ala Phe Lys Asn 
                725                 730                 735     


Glu Val Gly Val Leu Arg Lys Thr Arg His Val Asn Ile Leu Leu Phe 
            740                 745                 750         


Met Gly Tyr Ser Thr Lys Pro Gln Leu Ala Ile Val Thr Gln Trp Cys 
        755                 760                 765             


Glu Gly Ser Ser Leu Tyr His His Leu His Ile Ile Glu Thr Lys Phe 
    770                 775                 780                 


Glu Met Ile Lys Leu Ile Asp Ile Ala Arg Gln Thr Ala Gln Gly Met 
785                 790                 795                 800 


Asp Tyr Leu His Ala Lys Ser Ile Ile His Arg Asp Leu Lys Ser Asn 
                805                 810                 815     


Asn Ile Phe Leu His Glu Asp Leu Thr Val Lys Ile Gly Asp Phe Gly 
            820                 825                 830         


Leu Ala Thr Val Lys Ser Arg Trp Ser Gly Ser His Gln Phe Glu Gln 
        835                 840                 845             


Leu Ser Gly Ser Ile Leu Trp Met Ala Pro Glu Val Ile Arg Met Gln 
    850                 855                 860                 


Asp Lys Asn Pro Tyr Ser Phe Gln Ser Asp Val Tyr Ala Phe Gly Ile 
865                 870                 875                 880 


Val Leu Tyr Glu Leu Met Thr Gly Gln Leu Pro Tyr Ser Asn Ile Asn 
                885                 890                 895     


Asn Arg Asp Gln Ile Ile Phe Met Val Gly Arg Gly Tyr Leu Ser Pro 
            900                 905                 910         


Asp Leu Ser Lys Val Arg Ser Asn Cys Pro Lys Ala Met Lys Arg Leu 
        915                 920                 925             


Met Ala Glu Cys Leu Lys Lys Lys Arg Asp Glu Arg Pro Leu Phe Pro 
    930                 935                 940                 


Gln Ile Leu Ala Ser Ile Glu Leu Leu Ala Arg Ser Leu Pro Lys Ile 
945                 950                 955                 960 


His Arg Ser Ala Ser Glu Pro Ser Leu Asn Arg Ala Gly Phe Gln Thr 
                965                 970                 975     


Glu Asp Phe Ser Leu Tyr Ala Cys Ala Ser Pro Lys Thr Pro Ile Gln 
            980                 985                 990         


Ala Gly Gly Tyr Gly Ala Phe Pro  Val His 
        995                 1000         


