               SEQUENCE LISTING

<110> BAYER AG

<120> IMIDAZOTRIAZINE

<130> BHC 20 3 001 WO-PCT

<150> EP 20161681.0
<151> 2020-03-06

<160> 8

<170> BiSSAP 1.3.6

<210> 1
<211> 425
<212> PRT
<213> human 


<220> 
<223> His-CDK12

<400> 1
Met Thr Ser His His His His His His Ser Ser Met Gly Ser Arg Thr 
1               5                   10                  15      
Ser Leu Tyr Lys Lys Ala Gly Ser Asp Tyr Asp Ile Pro Thr Thr Glu 
            20                  25                  30          
Asn Leu Tyr Phe Gln Gly Gln Pro Tyr Lys Lys Arg Pro Lys Ile Cys 
        35                  40                  45              
Cys Pro Arg Tyr Gly Glu Arg Arg Gln Thr Glu Ser Asp Trp Gly Lys 
    50                  55                  60                  
Arg Cys Val Asp Lys Phe Asp Ile Ile Gly Ile Ile Gly Glu Gly Thr 
65                  70                  75                  80  
Tyr Gly Gln Val Tyr Lys Ala Lys Asp Lys Asp Thr Gly Glu Leu Val 
                85                  90                  95      
Ala Leu Lys Lys Val Arg Leu Asp Asn Glu Lys Glu Gly Phe Pro Ile 
            100                 105                 110         
Thr Ala Ile Arg Glu Ile Lys Ile Leu Arg Gln Leu Ile His Arg Ser 
        115                 120                 125             
Val Val Asn Met Lys Glu Ile Val Thr Asp Lys Gln Asp Ala Leu Asp 
    130                 135                 140                 
Phe Lys Lys Asp Lys Gly Ala Phe Tyr Leu Val Phe Glu Tyr Met Asp 
145                 150                 155                 160 
His Asp Leu Met Gly Leu Leu Glu Ser Gly Leu Val His Phe Ser Glu 
                165                 170                 175     
Asp His Ile Lys Ser Phe Met Lys Gln Leu Met Glu Gly Leu Glu Tyr 
            180                 185                 190         
Cys His Lys Lys Asn Phe Leu His Arg Asp Ile Lys Cys Ser Asn Ile 
        195                 200                 205             
Leu Leu Asn Asn Ser Gly Gln Ile Lys Leu Ala Asp Phe Gly Leu Ala 
    210                 215                 220                 
Arg Leu Tyr Asn Ser Glu Glu Ser Arg Pro Tyr Thr Asn Lys Val Ile 
225                 230                 235                 240 
Thr Leu Trp Tyr Arg Pro Pro Glu Leu Leu Leu Gly Glu Glu Arg Tyr 
                245                 250                 255     
Thr Pro Ala Ile Asp Val Trp Ser Cys Gly Cys Ile Leu Gly Glu Leu 
            260                 265                 270         
Phe Thr Lys Lys Pro Ile Phe Gln Ala Asn Leu Glu Leu Ala Gln Leu 
        275                 280                 285             
Glu Leu Ile Ser Arg Leu Cys Gly Ser Pro Cys Pro Ala Val Trp Pro 
    290                 295                 300                 
Asp Val Ile Lys Leu Pro Tyr Phe Asn Thr Met Lys Pro Lys Lys Gln 
305                 310                 315                 320 
Tyr Arg Arg Arg Leu Arg Glu Glu Phe Ser Phe Ile Pro Ser Ala Ala 
                325                 330                 335     
Leu Asp Leu Leu Asp His Met Leu Thr Leu Asp Pro Ser Lys Arg Cys 
            340                 345                 350         
Thr Ala Glu Gln Thr Leu Gln Ser Asp Phe Leu Lys Asp Val Glu Leu 
        355                 360                 365             
Ser Lys Met Ala Pro Pro Asp Leu Pro His Trp Gln Asp Cys His Glu 
    370                 375                 380                 
Leu Trp Ser Lys Lys Arg Arg Arg Gln Arg Gln Ser Gly Val Val Val 
385                 390                 395                 400 
Glu Glu Pro Pro Pro Ser Lys Thr Ser Arg Lys Glu Thr Thr Ser Gly 
                405                 410                 415     
Thr Ser Thr Glu Pro Val Lys Asn Ser 
            420                 425 

<210> 2
<211> 425
<212> PRT
<213> human 


<220> 
<223> His-CDK12-DN

<400> 2
Met Thr Ser His His His His His His Ser Ser Met Gly Ser Arg Thr 
1               5                   10                  15      
Ser Leu Tyr Lys Lys Ala Gly Ser Asp Tyr Asp Ile Pro Thr Thr Glu 
            20                  25                  30          
Asn Leu Tyr Phe Gln Gly Gln Pro Tyr Lys Lys Arg Pro Lys Ile Cys 
        35                  40                  45              
Cys Pro Arg Tyr Gly Glu Arg Arg Gln Thr Glu Ser Asp Trp Gly Lys 
    50                  55                  60                  
Arg Cys Val Asp Lys Phe Asp Ile Ile Gly Ile Ile Gly Glu Gly Thr 
65                  70                  75                  80  
Tyr Gly Gln Val Tyr Lys Ala Lys Asp Lys Asp Thr Gly Glu Leu Val 
                85                  90                  95      
Ala Leu Ala Lys Val Arg Leu Asp Asn Glu Lys Glu Gly Phe Pro Ile 
            100                 105                 110         
Thr Ala Ile Arg Glu Ile Lys Ile Leu Arg Gln Leu Ile His Arg Ser 
        115                 120                 125             
Val Val Asn Met Lys Glu Ile Val Thr Asp Lys Gln Asp Ala Leu Asp 
    130                 135                 140                 
Phe Lys Lys Asp Lys Gly Ala Phe Tyr Leu Val Phe Glu Tyr Met Asp 
145                 150                 155                 160 
His Asp Leu Met Gly Leu Leu Glu Ser Gly Leu Val His Phe Ser Glu 
                165                 170                 175     
Asp His Ile Lys Ser Phe Met Lys Gln Leu Met Glu Gly Leu Glu Tyr 
            180                 185                 190         
Cys His Lys Lys Asn Phe Leu His Arg Asp Ile Lys Cys Ser Asn Ile 
        195                 200                 205             
Leu Leu Asn Asn Ser Gly Gln Ile Lys Leu Ala Asn Phe Gly Leu Ala 
    210                 215                 220                 
Arg Leu Tyr Asn Ser Glu Glu Ser Arg Pro Tyr Thr Asn Lys Val Ile 
225                 230                 235                 240 
Thr Leu Trp Tyr Arg Pro Pro Glu Leu Leu Leu Gly Glu Glu Arg Tyr 
                245                 250                 255     
Thr Pro Ala Ile Asp Val Trp Ser Cys Gly Cys Ile Leu Gly Glu Leu 
            260                 265                 270         
Phe Thr Lys Lys Pro Ile Phe Gln Ala Asn Leu Glu Leu Ala Gln Leu 
        275                 280                 285             
Glu Leu Ile Ser Arg Leu Cys Gly Ser Pro Cys Pro Ala Val Trp Pro 
    290                 295                 300                 
Asp Val Ile Lys Leu Pro Tyr Phe Asn Thr Met Lys Pro Lys Lys Gln 
305                 310                 315                 320 
Tyr Arg Arg Arg Leu Arg Glu Glu Phe Ser Phe Ile Pro Ser Ala Ala 
                325                 330                 335     
Leu Asp Leu Leu Asp His Met Leu Thr Leu Asp Pro Ser Lys Arg Cys 
            340                 345                 350         
Thr Ala Glu Gln Thr Leu Gln Ser Asp Phe Leu Lys Asp Val Glu Leu 
        355                 360                 365             
Ser Lys Met Ala Pro Pro Asp Leu Pro His Trp Gln Asp Cys His Glu 
    370                 375                 380                 
Leu Trp Ser Lys Lys Arg Arg Arg Gln Arg Gln Ser Gly Val Val Val 
385                 390                 395                 400 
Glu Glu Pro Pro Pro Ser Lys Thr Ser Arg Lys Glu Thr Thr Ser Gly 
                405                 410                 415     
Thr Ser Thr Glu Pro Val Lys Asn Ser 
            420                 425 

<210> 3
<211> 425
<212> PRT
<213> human 


<220> 
<223> His-CDK13

<400> 3
Met Thr Ser His His His His His His Ser Ser Met Gly Ser Arg Thr 
1               5                   10                  15      
Ser Leu Tyr Lys Lys Ala Gly Ser Asp Tyr Asp Ile Pro Thr Thr Glu 
            20                  25                  30          
Asn Leu Tyr Phe Gln Gly Gln Leu His Ser Lys Arg Arg Pro Lys Ile 
        35                  40                  45              
Cys Gly Pro Arg Tyr Gly Glu Thr Lys Glu Lys Asp Ile Asp Trp Gly 
    50                  55                  60                  
Lys Arg Cys Val Asp Lys Phe Asp Ile Ile Gly Ile Ile Gly Glu Gly 
65                  70                  75                  80  
Thr Tyr Gly Gln Val Tyr Lys Ala Arg Asp Lys Asp Thr Gly Glu Met 
                85                  90                  95      
Val Ala Leu Lys Lys Val Arg Leu Asp Asn Glu Lys Glu Gly Phe Pro 
            100                 105                 110         
Ile Thr Ala Ile Arg Glu Ile Lys Ile Leu Arg Gln Leu Thr His Gln 
        115                 120                 125             
Ser Ile Ile Asn Met Lys Glu Ile Val Thr Asp Lys Glu Asp Ala Leu 
    130                 135                 140                 
Asp Phe Lys Lys Asp Lys Gly Ala Phe Tyr Leu Val Phe Glu Tyr Met 
145                 150                 155                 160 
Asp His Asp Leu Met Gly Leu Leu Glu Ser Gly Leu Val His Phe Asn 
                165                 170                 175     
Glu Asn His Ile Lys Ser Phe Met Arg Gln Leu Met Glu Gly Leu Asp 
            180                 185                 190         
Tyr Cys His Lys Lys Asn Phe Leu His Arg Asp Ile Lys Cys Ser Asn 
        195                 200                 205             
Ile Leu Leu Asn Asn Arg Gly Gln Ile Lys Leu Ala Asp Phe Gly Leu 
    210                 215                 220                 
Ala Arg Leu Tyr Ser Ser Glu Glu Ser Arg Pro Tyr Thr Asn Lys Val 
225                 230                 235                 240 
Ile Thr Leu Trp Tyr Arg Pro Pro Glu Leu Leu Leu Gly Glu Glu Arg 
                245                 250                 255     
Tyr Thr Pro Ala Ile Asp Val Trp Ser Cys Gly Cys Ile Leu Gly Glu 
            260                 265                 270         
Leu Phe Thr Lys Lys Pro Ile Phe Gln Ala Asn Gln Glu Leu Ala Gln 
        275                 280                 285             
Leu Glu Leu Ile Ser Arg Ile Cys Gly Ser Pro Cys Pro Ala Val Trp 
    290                 295                 300                 
Pro Asp Val Ile Lys Leu Pro Tyr Phe Asn Thr Met Lys Pro Lys Lys 
305                 310                 315                 320 
Gln Tyr Arg Arg Lys Leu Arg Glu Glu Phe Val Phe Ile Pro Ala Ala 
                325                 330                 335     
Ala Leu Asp Leu Phe Asp Tyr Met Leu Ala Leu Asp Pro Ser Lys Arg 
            340                 345                 350         
Cys Thr Ala Glu Gln Ala Leu Gln Cys Glu Phe Leu Arg Asp Val Glu 
        355                 360                 365             
Pro Ser Lys Met Pro Pro Pro Asp Leu Pro Leu Trp Gln Asp Cys His 
    370                 375                 380                 
Glu Leu Trp Ser Lys Lys Arg Arg Arg Gln Lys Gln Met Gly Met Thr 
385                 390                 395                 400 
Asp Asp Val Ser Thr Ile Lys Ala Pro Arg Lys Asp Leu Ser Leu Gly 
                405                 410                 415     
Leu Asp Asp Ser Arg Thr Asn Thr Pro 
            420                 425 

<210> 4
<211> 425
<212> PRT
<213> human 


<220> 
<223> His-CDK13-DN

<400> 4
Met Thr Ser His His His His His His Ser Ser Met Gly Ser Arg Thr 
1               5                   10                  15      
Ser Leu Tyr Lys Lys Ala Gly Ser Asp Tyr Asp Ile Pro Thr Thr Glu 
            20                  25                  30          
Asn Leu Tyr Phe Gln Gly Gln Leu His Ser Lys Arg Arg Pro Lys Ile 
        35                  40                  45              
Cys Gly Pro Arg Tyr Gly Glu Thr Lys Glu Lys Asp Ile Asp Trp Gly 
    50                  55                  60                  
Lys Arg Cys Val Asp Lys Phe Asp Ile Ile Gly Ile Ile Gly Glu Gly 
65                  70                  75                  80  
Thr Tyr Gly Gln Val Tyr Lys Ala Arg Asp Lys Asp Thr Gly Glu Met 
                85                  90                  95      
Val Ala Leu Ala Lys Val Arg Leu Asp Asn Glu Lys Glu Gly Phe Pro 
            100                 105                 110         
Ile Thr Ala Ile Arg Glu Ile Lys Ile Leu Arg Gln Leu Thr His Gln 
        115                 120                 125             
Ser Ile Ile Asn Met Lys Glu Ile Val Thr Asp Lys Glu Asp Ala Leu 
    130                 135                 140                 
Asp Phe Lys Lys Asp Lys Gly Ala Phe Tyr Leu Val Phe Glu Tyr Met 
145                 150                 155                 160 
Asp His Asp Leu Met Gly Leu Leu Glu Ser Gly Leu Val His Phe Asn 
                165                 170                 175     
Glu Asn His Ile Lys Ser Phe Met Arg Gln Leu Met Glu Gly Leu Asp 
            180                 185                 190         
Tyr Cys His Lys Lys Asn Phe Leu His Arg Asp Ile Lys Cys Ser Asn 
        195                 200                 205             
Ile Leu Leu Asn Asn Arg Gly Gln Ile Lys Leu Ala Asn Phe Gly Leu 
    210                 215                 220                 
Ala Arg Leu Tyr Ser Ser Glu Glu Ser Arg Pro Tyr Thr Asn Lys Val 
225                 230                 235                 240 
Ile Thr Leu Trp Tyr Arg Pro Pro Glu Leu Leu Leu Gly Glu Glu Arg 
                245                 250                 255     
Tyr Thr Pro Ala Ile Asp Val Trp Ser Cys Gly Cys Ile Leu Gly Glu 
            260                 265                 270         
Leu Phe Thr Lys Lys Pro Ile Phe Gln Ala Asn Gln Glu Leu Ala Gln 
        275                 280                 285             
Leu Glu Leu Ile Ser Arg Ile Cys Gly Ser Pro Cys Pro Ala Val Trp 
    290                 295                 300                 
Pro Asp Val Ile Lys Leu Pro Tyr Phe Asn Thr Met Lys Pro Lys Lys 
305                 310                 315                 320 
Gln Tyr Arg Arg Lys Leu Arg Glu Glu Phe Val Phe Ile Pro Ala Ala 
                325                 330                 335     
Ala Leu Asp Leu Phe Asp Tyr Met Leu Ala Leu Asp Pro Ser Lys Arg 
            340                 345                 350         
Cys Thr Ala Glu Gln Ala Leu Gln Cys Glu Phe Leu Arg Asp Val Glu 
        355                 360                 365             
Pro Ser Lys Met Pro Pro Pro Asp Leu Pro Leu Trp Gln Asp Cys His 
    370                 375                 380                 
Glu Leu Trp Ser Lys Lys Arg Arg Arg Gln Lys Gln Met Gly Met Thr 
385                 390                 395                 400 
Asp Asp Val Ser Thr Ile Lys Ala Pro Arg Lys Asp Leu Ser Leu Gly 
                405                 410                 415     
Leu Asp Asp Ser Arg Thr Asn Thr Pro 
            420                 425 

<210> 5
<211> 338
<212> PRT
<213> human 


<220> 
<223> His-CycK

<400> 5
Met Thr Ser His His His His His His Ser Ser Met Gly Ser Arg Thr 
1               5                   10                  15      
Ser Leu Tyr Lys Lys Ala Gly Ser Asp Tyr Asp Ile Pro Thr Thr Glu 
            20                  25                  30          
Asn Leu Tyr Phe Gln Gly Met Lys Glu Asn Lys Glu Asn Ser Ser Pro 
        35                  40                  45              
Ser Val Thr Ser Ala Asn Leu Asp His Thr Lys Pro Cys Trp Tyr Trp 
    50                  55                  60                  
Asp Lys Lys Asp Leu Ala His Thr Pro Ser Gln Leu Glu Gly Leu Asp 
65                  70                  75                  80  
Pro Ala Thr Glu Ala Arg Tyr Arg Arg Glu Gly Ala Arg Phe Ile Phe 
                85                  90                  95      
Asp Val Gly Thr Arg Leu Gly Leu His Tyr Asp Thr Leu Ala Thr Gly 
            100                 105                 110         
Ile Ile Tyr Phe His Arg Phe Tyr Met Phe His Ser Phe Lys Gln Phe 
        115                 120                 125             
Pro Arg Tyr Val Thr Gly Ala Cys Cys Leu Phe Leu Ala Gly Lys Val 
    130                 135                 140                 
Glu Glu Thr Pro Lys Lys Cys Lys Asp Ile Ile Lys Thr Ala Arg Ser 
145                 150                 155                 160 
Leu Leu Asn Asp Val Gln Phe Gly Gln Phe Gly Asp Asp Pro Lys Glu 
                165                 170                 175     
Glu Val Met Val Leu Glu Arg Ile Leu Leu Gln Thr Ile Lys Phe Asp 
            180                 185                 190         
Leu Gln Val Glu His Pro Tyr Gln Phe Leu Leu Lys Tyr Ala Lys Gln 
        195                 200                 205             
Leu Lys Gly Asp Lys Asn Lys Ile Gln Lys Leu Val Gln Met Ala Trp 
    210                 215                 220                 
Thr Phe Val Asn Asp Ser Leu Cys Thr Thr Leu Ser Leu Gln Trp Glu 
225                 230                 235                 240 
Pro Glu Ile Ile Ala Val Ala Val Met Tyr Leu Ala Gly Arg Leu Cys 
                245                 250                 255     
Lys Phe Glu Ile Gln Glu Trp Thr Ser Lys Pro Met Tyr Arg Arg Trp 
            260                 265                 270         
Trp Glu Gln Phe Val Gln Asp Val Pro Val Asp Val Leu Glu Asp Ile 
        275                 280                 285             
Cys His Gln Ile Leu Asp Leu Tyr Ser Gln Gly Lys Gln Gln Met Pro 
    290                 295                 300                 
His His Thr Pro His Gln Leu Gln Gln Pro Pro Ser Leu Gln Pro Thr 
305                 310                 315                 320 
Pro Gln Val Pro Gln Val Gln Gln Ser Gln Pro Ser Gln Ser Ser Glu 
                325                 330                 335     
Pro Ser 
        

<210> 6
<211> 368
<212> PRT
<213> saccharomyces cerevisiae 


<220> 
<223> CAK1

<400> 6
Met Lys Leu Asp Ser Ile Asp Ile Thr His Cys Gln Leu Val Lys Ser 
1               5                   10                  15      
Thr Arg Thr Ala Arg Ile Tyr Arg Ser Asp Thr Tyr Ala Ile Lys Cys 
            20                  25                  30          
Leu Ala Leu Asp Phe Asp Ile Pro Pro His Asn Ala Lys Phe Glu Val 
        35                  40                  45              
Ser Ile Leu Asn Lys Leu Gly Asn Lys Cys Lys His Ile Leu Pro Leu 
    50                  55                  60                  
Leu Glu Ser Lys Ala Thr Asp Asn Asn Asp Leu Leu Leu Leu Phe Pro 
65                  70                  75                  80  
Phe Glu Glu Met Asn Leu Tyr Glu Phe Met Gln Met His Tyr Lys Arg 
                85                  90                  95      
Asp Arg Arg Lys Lys Asn Pro Tyr Tyr Asp Leu Leu Asn Pro Ser Ile 
            100                 105                 110         
Pro Ile Val Ala Asp Pro Pro Val Gln Lys Tyr Thr Asn Gln Leu Asp 
        115                 120                 125             
Val Asn Arg Tyr Ser Leu Ser Phe Phe Arg Gln Met Val Glu Gly Ile 
    130                 135                 140                 
Ala Phe Leu His Glu Asn Lys Ile Ile His Arg Asp Ile Lys Pro Gln 
145                 150                 155                 160 
Asn Ile Met Leu Thr Asn Asn Thr Ser Thr Val Ser Pro Lys Leu Tyr 
                165                 170                 175     
Ile Ile Asp Phe Gly Ile Ser Tyr Asp Met Ala Asn Asn Ser Gln Thr 
            180                 185                 190         
Ser Ala Glu Pro Met Asp Ser Lys Val Thr Asp Ile Ser Thr Gly Ile 
        195                 200                 205             
Tyr Lys Ala Pro Glu Val Leu Phe Gly Val Lys Cys Tyr Asp Gly Gly 
    210                 215                 220                 
Val Asp Val Trp Ser Leu Leu Ile Ile Ile Ser Gln Trp Phe Gln Arg 
225                 230                 235                 240 
Glu Thr Ser Arg Met Gly His Val Pro Ala Met Ile Asp Asp Gly Ser 
                245                 250                 255     
Asp Asp Met Asn Ser Asp Gly Ser Asp Phe Arg Leu Ile Cys Ser Ile 
            260                 265                 270         
Phe Glu Lys Leu Gly Ile Pro Ser Ile Gln Lys Trp Glu Glu Val Ala 
        275                 280                 285             
Gln His Gly Ser Val Asp Ala Phe Val Gly Met Phe Gly Ala Asp Gly 
    290                 295                 300                 
Asp Gly Lys Tyr Val Leu Asp Gln Glu Lys Asp Val Gln Ile Ser Ile 
305                 310                 315                 320 
Val Glu Arg Asn Met Pro Arg Leu Asp Glu Ile Ala Asp Val Lys Val 
                325                 330                 335     
Lys Gln Lys Phe Ile Asn Cys Ile Leu Gly Met Val Ser Phe Ser Pro 
            340                 345                 350         
Asn Glu Arg Trp Ser Cys Gln Arg Ile Leu Gln Glu Leu Glu Lys Pro 
        355                 360                 365             



<210> 7
<211> 18
<212> PRT
<213> human 


<220> 
<223> biotinylated peptide biotin-Ahx, C-terminus in amid form

<400> 7
Lys Phe Glu Leu Leu Pro Thr Pro Pro Leu Ser Pro Ser Arg Arg Ser 
1               5                   10                  15      
Gly Leu 
        

<210> 8
<211> 14
<212> PRT
<213> human 


<220> 
<223> biotinylated peptide biotin-Ttds, C-terminus in amid form

<400> 8
Tyr Ile Ser Pro Leu Lys Ser Pro Tyr Lys Ile Ser Glu Gly 
1               5                   10                  

