                         SEQUENCE LISTING

<110>  Eli Lilly and Company
 
<120>  USE OF AN MMP28 INHIBITOR FOR INCREASING MYELINATION

<130>  X17508

<140>  60/976570
<141>  2007-04-18

<160>  9     

<170>  PatentIn version 3.4

<210>  1
<211>  520
<212>  PRT
<213>  homo sapiens

<400>  1

Met Val Ala Arg Val Gly Leu Leu Leu Arg Ala Leu Gln Leu Leu Leu 
1               5                   10                  15      


Trp Gly His Leu Asp Ala Gln Pro Ala Glu Arg Gly Gly Gln Glu Leu 
            20                  25                  30          


Arg Lys Glu Ala Glu Ala Phe Leu Glu Lys Tyr Gly Tyr Leu Asn Glu 
        35                  40                  45              


Gln Val Pro Lys Ala Pro Thr Ser Thr Arg Phe Ser Asp Ala Ile Arg 
    50                  55                  60                  


Ala Phe Gln Trp Val Ser Gln Leu Pro Val Ser Gly Val Leu Asp Arg 
65                  70                  75                  80  


Ala Thr Leu Arg Gln Met Thr Arg Pro Arg Cys Gly Val Thr Asp Thr 
                85                  90                  95      


Asn Ser Tyr Ala Ala Trp Ala Glu Arg Ile Ser Asp Leu Phe Ala Arg 
            100                 105                 110         


His Arg Thr Lys Met Arg Arg Lys Lys Arg Phe Ala Lys Gln Gly Asn 
        115                 120                 125             


Lys Trp Tyr Lys Gln His Leu Ser Tyr Arg Leu Val Asn Trp Pro Glu 
    130                 135                 140                 


His Leu Pro Glu Pro Ala Val Arg Gly Ala Val Arg Ala Ala Phe Gln 
145                 150                 155                 160 


Leu Trp Ser Asn Val Ser Ala Leu Glu Phe Trp Glu Ala Pro Ala Thr 
                165                 170                 175     


Gly Pro Ala Asp Ile Arg Leu Thr Phe Phe Gln Gly Asp His Asn Asp 
            180                 185                 190         


Gly Leu Gly Asn Ala Phe Asp Gly Pro Gly Gly Ala Leu Ala His Ala 
        195                 200                 205             


Phe Leu Pro Arg Arg Gly Glu Ala His Phe Asp Gln Asp Glu Arg Trp 
    210                 215                 220                 


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


Glu Ile Gly His Thr Leu Gly Leu Thr His Ser Pro Ala Pro Arg Ala 
                245                 250                 255     


Leu Met Ala Pro Tyr Tyr Lys Arg Leu Gly Arg Asp Ala Leu Leu Ser 
            260                 265                 270         


Trp Asp Asp Val Leu Ala Val Gln Ser Leu Tyr Gly Lys Pro Leu Gly 
        275                 280                 285             


Gly Ser Val Ala Val Gln Leu Pro Gly Lys Leu Phe Thr Asp Phe Glu 
    290                 295                 300                 


Thr Trp Asp Ser Tyr Ser Pro Gln Gly Arg Arg Pro Glu Thr Gln Gly 
305                 310                 315                 320 


Pro Lys Tyr Cys His Ser Ser Phe Asp Ala Ile Thr Val Asp Arg Gln 
                325                 330                 335     


Gln Gln Leu Tyr Ile Phe Lys Gly Ser His Phe Trp Glu Val Ala Ala 
            340                 345                 350         


Asp Gly Asn Val Ser Glu Pro Arg Pro Leu Gln Glu Arg Trp Val Gly 
        355                 360                 365             


Leu Pro Pro Asn Ile Glu Ala Ala Ala Val Ser Leu Asn Asp Gly Asp 
    370                 375                 380                 


Phe Tyr Phe Phe Lys Gly Gly Arg Cys Trp Arg Phe Arg Gly Pro Lys 
385                 390                 395                 400 


Pro Val Trp Gly Leu Pro Gln Leu Cys Arg Ala Gly Gly Leu Pro Arg 
                405                 410                 415     


His Pro Asp Ala Ala Leu Phe Phe Pro Pro Leu Arg Arg Leu Ile Leu 
            420                 425                 430         


Phe Lys Gly Ala Arg Tyr Tyr Val Leu Ala Arg Gly Gly Leu Gln Val 
        435                 440                 445             


Glu Pro Tyr Tyr Pro Arg Ser Leu Gln Asp Trp Gly Gly Ile Pro Glu 
    450                 455                 460                 


Glu Val Ser Gly Ala Leu Pro Arg Pro Asp Gly Ser Ile Ile Phe Phe 
465                 470                 475                 480 


Arg Asp Asp Arg Tyr Trp Arg Leu Asp Gln Ala Lys Leu Gln Ala Thr 
                485                 490                 495     


Thr Ser Gly Arg Trp Ala Thr Glu Leu Pro Trp Met Gly Cys Trp His 
            500                 505                 510         


Ala Asn Ser Gly Ser Ala Leu Phe 
        515                 520 


<210>  2
<211>  17
<212>  PRT
<213>  homo sapiens

<400>  2

Phe Ala Lys Gln Gly Asn Lys Trp Tyr Lys Gln His Leu Ser Tyr Arg 
1               5                   10                  15      


Leu 
    


<210>  3
<211>  11
<212>  PRT
<213>  homo sapiens

<400>  3

Lys Arg Leu Gly Arg Asp Ala Leu Leu Ser Trp 
1               5                   10      


<210>  4
<211>  496
<212>  PRT
<213>  xenopus laevis

<400>  4

Met Glu Ala Asp Ile Pro Ser Leu Phe Leu Leu Leu Val Ile Thr Gly 
1               5                   10                  15      


Leu Cys Leu Cys Asn Gly Tyr Ile Ser Glu Glu Thr Leu Gln Thr Ala 
            20                  25                  30          


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


His Ser Gly Lys Gln Leu Ala Ser Ala Val Arg Glu Phe Gln Trp Leu 
    50                  55                  60                  


Ser His Leu Ser Val Ser Gly Glu Leu Asp Thr Ser Thr Val Gln Gln 
65                  70                  75                  80  


Met Ile Gln Pro Arg Cys Gly Val Lys Asp Ile Glu Ser Leu Lys Leu 
                85                  90                  95      


Val Lys Ser His His His Gly Arg Gln Arg Lys Lys Arg Tyr Ile Ser 
            100                 105                 110         


Lys Ser Lys Lys Trp Tyr Lys Gln His Leu Thr Tyr Gln Ile Val Asn 
        115                 120                 125             


Trp Pro Trp Tyr Leu Ser Gln His Gln Val Arg Gln Ala Val Lys Ala 
    130                 135                 140                 


Ala Phe Gln Leu Trp Ser Asn Val Ser Ser Leu Thr Phe Ser Glu Ala 
145                 150                 155                 160 


Leu Arg Asp Pro Ala Asp Ile Arg Leu Ala Phe Phe Asp Gly Asp His 
                165                 170                 175     


Asn Asp Gly Ala Gly Asn Ala Phe Asp Gly Pro Gly Gly Ala Leu Ala 
            180                 185                 190         


His Ala Phe Phe Pro Arg Arg Gly Glu Ala His Phe Asp Ser Ala Glu 
        195                 200                 205             


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


His Glu Ile Gly His Thr Leu Gly Leu Pro His Ser Ser Phe Lys Asn 
225                 230                 235                 240 


Ala Leu Met Ser Pro Tyr Tyr Lys Lys Leu Asn Lys Asp Tyr Val Leu 
                245                 250                 255     


Asn Phe Asp Asp Val Leu Ala Ile Gln Asn Leu Tyr Gly Ala Pro Pro 
            260                 265                 270         


Ser Gly Asn Leu Val Gln Leu Pro Gly Lys Gln Phe Ala Phe Phe Gln 
        275                 280                 285             


Asp Trp Ser Pro Glu Ser His Glu Asp Ser Gly Met Lys Pro Ser Tyr 
    290                 295                 300                 


Cys His Ser Ile Phe Asp Ala Ile Thr Trp Asp Leu Lys Lys Thr Leu 
305                 310                 315                 320 


Tyr Ile Phe Lys Gly Arg His Phe Trp Met Val Ser Leu Gly Gly Lys 
                325                 330                 335     


Ile Ser Pro Pro Gln Ser Leu Gln Lys Arg Trp Lys Lys Leu Pro Ser 
            340                 345                 350         


Tyr Ile Glu Ala Ala Val Val Ser Gly Leu Asp Gly Lys Phe Tyr Phe 
        355                 360                 365             


Phe Lys Gly Gly Arg Cys Trp Arg Tyr Lys Asp Ser Ile Leu Glu Glu 
    370                 375                 380                 


Gly Phe Pro Gln Lys Cys Ser Met Asn Gly Leu Pro Arg Arg Pro Asp 
385                 390                 395                 400 


Thr Ala Leu Tyr Phe Gln Pro Leu Gly His Leu Val Ile Phe Lys Gly 
                405                 410                 415     


Ser Lys Tyr Tyr Val Val Asn Glu Glu Ser Leu Thr Val Glu Pro Tyr 
            420                 425                 430         


Tyr Pro Arg Ser Leu Asp His Trp Lys Gly Val Pro Ala Asn Ser His 
        435                 440                 445             


Ser Val Leu Thr His Pro Asp Gly Ala Ile Tyr Phe Phe Lys Gly His 
    450                 455                 460                 


Gln Tyr Trp Ile Phe Asp Gln Lys Lys Leu Lys Val Thr Thr Ser Gly 
465                 470                 475                 480 


Lys Trp Ala Glu Asp Leu Ser Trp Ile Gly Cys Lys Asn Asp Val Thr 
                485                 490                 495     


<210>  5
<211>  520
<212>  PRT
<213>  mus musculus

<400>  5

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


Trp Gly Cys Gln Asp Ala Gln Pro Thr Gln His Gly Leu Pro Glu Leu 
            20                  25                  30          


Arg Gln Glu Ala Glu Ala Phe Leu Glu Lys Tyr Gly Tyr Leu Ser Glu 
        35                  40                  45              


Gln Gly Ser Lys Ala Pro Ala Ser Ala Gln Phe Arg Asn Ala Ile Arg 
    50                  55                  60                  


Glu Phe Gln Trp Ile Ser Gln Leu Pro Leu Ser Gly Val Leu Asp Gln 
65                  70                  75                  80  


Ala Thr Leu Arg Gln Met Thr Arg Pro Arg Cys Gly Val Ala Asp Thr 
                85                  90                  95      


Asp Ser His Ala Thr Trp Thr Glu Arg Ile Ser Thr Leu Leu Ala Gly 
            100                 105                 110         


His Arg Ala Lys Met Arg Arg Lys Lys Arg Phe Ala Lys Pro Gly Asn 
        115                 120                 125             


Lys Trp Tyr Lys Gln His Leu Ser Tyr Arg Leu Val Asn Trp Pro Glu 
    130                 135                 140                 


Arg Leu Pro Glu Pro Ala Val Arg Gly Ala Val Arg Ala Ala Phe Gln 
145                 150                 155                 160 


Leu Trp Ser Asn Val Ser Ala Leu Glu Phe Trp Glu Ala Pro Ala Thr 
                165                 170                 175     


Gly Pro Ala Asp Ile Arg Leu Thr Phe Phe Gln Gly Asp His Asn Asp 
            180                 185                 190         


Gly Leu Ala Asn Ala Phe Asp Gly Pro Gly Gly Ala Leu Ala His Ala 
        195                 200                 205             


Phe Leu Pro Arg Arg Gly Glu Ala His Phe Asp Gly Asp Glu Arg Trp 
    210                 215                 220                 


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


Glu Ile Gly His Thr Leu Gly Leu Thr His Ser Pro Ala Pro Arg Ala 
                245                 250                 255     


Leu Met Ala Pro Tyr Tyr Lys Lys Leu Gly Arg Asp Ala Leu Leu Ser 
            260                 265                 270         


Trp Asp Asp Val Leu Ala Val Gln Ser Leu Tyr Gly Lys Pro Leu Gly 
        275                 280                 285             


Arg Ser Val Ala Thr Gln Leu Pro Gly Lys Val Phe Thr Asp Phe Glu 
    290                 295                 300                 


Ala Trp Asp Pro His Asn Ser Gln Ser Arg Arg Pro Glu Thr Arg Gly 
305                 310                 315                 320 


Pro Lys Tyr Cys His Ser Ser Phe Asp Ala Ile Thr Val Asp Gly Gln 
                325                 330                 335     


Trp Arg Leu Tyr Val Phe Lys Gly Ser Tyr Phe Trp Glu Val Thr Val 
            340                 345                 350         


Asp Gly Asn Val Ser Glu Pro Arg Pro Leu Gln Lys Arg Trp Pro Gly 
        355                 360                 365             


Leu Pro Pro Gly Ile Glu Ala Ala Ala Val Ser Leu Glu Asp Gly Asp 
    370                 375                 380                 


Phe Tyr Phe Phe Lys Gly Asn Arg Cys Trp Arg Phe Gln Gly Thr Lys 
385                 390                 395                 400 


Ser Val Trp Gly Phe Ala Gln Leu Cys Arg Ala Gly Gly Leu Pro Arg 
                405                 410                 415     


His Pro Asp Ala Ala Leu Phe Phe Pro Pro Leu Arg Arg Leu Val Leu 
            420                 425                 430         


Phe Lys Gly Ser Arg Tyr Tyr Val Leu Ala Gln Gly Gly Met Gln Val 
        435                 440                 445             


Glu Pro Tyr Tyr Pro Arg Ser Leu Arg Asp Trp Ala Gly Val Pro Glu 
    450                 455                 460                 


Glu Val Ser Gly Ala Leu Pro Arg Pro Asp Gly Ser Ile Ile Phe Phe 
465                 470                 475                 480 


Arg Asp Asp His Tyr Trp His Leu Asp Gln Ala Lys Leu Arg Val Thr 
                485                 490                 495     


Ser Ser Gly Arg Trp Ala Thr Glu Leu Ser Trp Met Gly Cys Trp Asn 
            500                 505                 510         


Ala Asn Ser Gly Gly Ala Leu Phe 
        515                 520 


<210>  6
<211>  524
<212>  PRT
<213>  Rattus rattus

<400>  6

Met Val Thr Gly Leu Ser Leu Leu Leu Arg Val Leu Pro Leu Leu Leu 
1               5                   10                  15      


Trp Gly Cys Gln Asp Ala Gln Pro Thr Pro Arg Gly His Pro Glu Leu 
            20                  25                  30          


His Gln Glu Ala Glu Ala Phe Leu Glu Lys Tyr Gly Tyr Leu Ser Glu 
        35                  40                  45              


Gln Gly Lys Val Pro Ala Ser Thr Gln Phe Ser Asp Ala Ile Arg Glu 
    50                  55                  60                  


Phe Gln Trp Val Ser Gln Leu Pro Ile Ser Gly Val Leu Asp Arg Ala 
65                  70                  75                  80  


Thr Leu Arg Gln Met Thr Arg Pro Arg Cys Gly Val Ala Asp Thr Asp 
                85                  90                  95      


Ser His Glu Thr Trp Thr Glu Arg Ile Arg Ala Leu Leu Ala Gly His 
            100                 105                 110         


Arg Ala Lys Met Arg Arg Lys Lys Arg Phe Ala Lys Pro Gly His Lys 
        115                 120                 125             


Trp Tyr Lys Gln His Leu Ser Tyr Arg Leu Val Asn Trp Pro Lys Ser 
    130                 135                 140                 


Leu Pro Glu Pro Ala Val Arg Gly Ala Val Arg Ala Ala Phe Gln Leu 
145                 150                 155                 160 


Trp Ser Asn Val Ser Ala Leu Glu Phe Trp Glu Ala Pro Ala Thr Gly 
                165                 170                 175     


Pro Ala Asp Ile Arg Leu Thr Phe Phe Gln Gly Asp His Asn Asp Gly 
            180                 185                 190         


Leu Ala Asn Ala Phe Asp Gly Pro Gly Gly Ala Leu Ala His Ala Phe 
        195                 200                 205             


Leu Pro Arg Arg Gly Glu Ala His Phe Asp Gln Asp Glu Arg Trp Ser 
    210                 215                 220                 


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


Ile Gly His Thr Leu Gly Leu Thr His Ser Pro Ala Pro Arg Ala Leu 
                245                 250                 255     


Met Ala Pro Tyr Tyr Lys Lys Leu Gly Arg Asp Ala Leu Leu Ser Trp 
            260                 265                 270         


Asp Asp Val Leu Ala Val Gln Asn Leu Tyr Gly Lys Pro Leu Gly Arg 
        275                 280                 285             


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


Trp Asp Pro His Asn Ser Gln Ser Arg Arg Pro Glu Thr Arg Gly Pro 
305                 310                 315                 320 


Lys Tyr Cys His Ser Ser Phe Asp Ala Ile Thr Val Asp Gly Gln Trp 
                325                 330                 335     


Arg Leu Tyr Val Phe Lys Gly Ser His Phe Trp Glu Val Thr Ala Asp 
            340                 345                 350         


Gly Asn Val Ser Glu Pro His Pro Leu Gln Lys Arg Trp Pro Gly Leu 
        355                 360                 365             


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


Phe Phe Phe Lys Gly Asn Arg Cys Trp Arg Phe Gln Gly Thr Lys Ser 
385                 390                 395                 400 


Val Phe Ala Gln Leu Cys Arg Ala Gly Gly Leu Pro Arg His Pro Asp 
                405                 410                 415     


Ala Ala Leu Phe Phe Pro Pro Leu Arg Arg Leu Val Leu Phe Lys Gly 
            420                 425                 430         


Ser Arg Tyr Tyr Val Leu Ala Arg Gly Gly Met Gln Val Glu Pro Tyr 
        435                 440                 445             


Tyr Pro Arg Ser Leu Arg Asp Trp Ala Gly Val Pro Glu Glu Val Ser 
    450                 455                 460                 


Gly Ala Leu Pro Arg Pro Asp Gly Ser Ile Ile Phe Phe Arg Asp Asp 
465                 470                 475                 480 


His Tyr Trp His Leu Asp Gln Ala Lys Leu Arg Val Thr Ser Ser Gly 
                485                 490                 495     


Arg Trp Ala Thr Glu Leu Ser Trp Met Gly Cys Trp Asn Ala Asn Ser 
            500                 505                 510         


Gly Gly Ala Leu Phe Gln Arg Leu Pro Val Thr Glu 
        515                 520                 


<210>  7
<211>  398
<212>  PRT
<213>  homo sapiens

<400>  7

Phe Ala Lys Gln Gly Asn Lys Trp Tyr Lys Gln His Leu Ser Tyr Arg 
1               5                   10                  15      


Leu Val Asn Trp Pro Glu His Leu Pro Glu Pro Ala Val Arg Gly Ala 
            20                  25                  30          


Val Arg Ala Ala Phe Gln Leu Trp Ser Asn Val Ser Ala Leu Glu Phe 
        35                  40                  45              


Trp Glu Ala Pro Ala Thr Gly Pro Ala Asp Ile Arg Leu Thr Phe Phe 
    50                  55                  60                  


Gln Gly Asp His Asn Asp Gly Leu Gly Asn Ala Phe Asp Gly Pro Gly 
65                  70                  75                  80  


Gly Ala Leu Ala His Ala Phe Leu Pro Arg Arg Gly Glu Ala His Phe 
                85                  90                  95      


Asp Gln Asp Glu Arg Trp Ser Leu Ser Arg Arg Arg Gly Arg Asn Leu 
            100                 105                 110         


Phe Val Val Leu Ala His Glu Ile Gly His Thr Leu Gly Leu Thr His 
        115                 120                 125             


Ser Pro Ala Pro Arg Ala Leu Met Ala Pro Tyr Tyr Lys Arg Leu Gly 
    130                 135                 140                 


Arg Asp Ala Leu Leu Ser Trp Asp Asp Val Leu Ala Val Gln Ser Leu 
145                 150                 155                 160 


Tyr Gly Lys Pro Leu Gly Gly Ser Val Ala Val Gln Leu Pro Gly Lys 
                165                 170                 175     


Leu Phe Thr Asp Phe Glu Thr Trp Asp Ser Tyr Ser Pro Gln Gly Arg 
            180                 185                 190         


Arg Pro Glu Thr Gln Gly Pro Lys Tyr Cys His Ser Ser Phe Asp Ala 
        195                 200                 205             


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


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


Gln Glu Arg Trp Val Gly Leu Pro Pro Asn Ile Glu Ala Ala Ala Val 
                245                 250                 255     


Ser Leu Asn Asp Gly Asp Phe Tyr Phe Phe Lys Gly Gly Arg Cys Trp 
            260                 265                 270         


Arg Phe Arg Gly Pro Lys Pro Val Trp Gly Leu Pro Gln Leu Cys Arg 
        275                 280                 285             


Ala Gly Gly Leu Pro Arg His Pro Asp Ala Ala Leu Phe Phe Pro Pro 
    290                 295                 300                 


Leu Arg Arg Leu Ile Leu Phe Lys Gly Ala Arg Tyr Tyr Val Leu Ala 
305                 310                 315                 320 


Arg Gly Gly Leu Gln Val Glu Pro Tyr Tyr Pro Arg Ser Leu Gln Asp 
                325                 330                 335     


Trp Gly Gly Ile Pro Glu Glu Val Ser Gly Ala Leu Pro Arg Pro Asp 
            340                 345                 350         


Gly Ser Ile Ile Phe Phe Arg Asp Asp Arg Tyr Trp Cys Leu Asp Gln 
        355                 360                 365             


Ala Lys Leu Gln Ala Thr Thr Ser Gly Arg Trp Ala Thr Glu Leu Pro 
    370                 375                 380                 


Trp Met Gly Cys Trp His Ala Asn Ser Gly Ser Ala Leu Phe 
385                 390                 395             


<210>  8
<211>  18
<212>  PRT
<213>  xenopus laevis

<400>  8

Lys Ser Glu Pro Gln Glu Ser Glu Ala Lys Pro Ala Pro Thr Glu Val 
1               5                   10                  15      


Lys Thr 
        


<210>  9
<211>  28
<212>  PRT
<213>  xenopus laevis

<400>  9

Arg Gly Ser Gly Ser Val Asp Glu Thr Leu Phe Ala Leu Pro Ala Ala 
1               5                   10                  15      


Ser Glu Pro Val Ile Pro Ser Ser Ala Glu Lys Ile 
            20                  25              


