                         SEQUENCE LISTING

<110>  Roxas-Duncan, Virginia I
       Smith, Leonard A
       Gul, Nizamettin
       Yang, David
       Enyedy, Istvan
       Dakshanamurthy, Sivanesan
       Shah, Salim
       Cardellina, John  II
       Vieira, Rebecca C
       Ensel, Susan M
 
<120>  SMALL MOLECULE INHIBITORS OF BOTULINUM NEUROTOXIN

<130>  048093-132924

<160>  8     

<170>  PatentIn version 3.5

<210>  1
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide inhibitor of Clostridium botulism neurotoxin serotype A 
       commercially available from EMD Chemicals Inc.


<220>
<221>  MISC_FEATURE
<223>  The n-terminal contains a variable acetyl sequence

<220>
<221>  MISC_FEATURE
<223>  The c-terminal contains an amino group

<400>  1

Cys Arg Ala Thr Lys Met Leu 
1               5           


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


<220>
<221>  MISC_FEATURE
<223>  The n-terminal contains a variable acetyl sequence

<220>
<221>  MISC_FEATURE
<223>  The c-terminal contains an amino group

<400>  2

Ser Asn Lys Thr Arg Ile Asp Glu Ala Asn Gln Arg Ala Thr Lys Met 
1               5                   10                  15      


Leu 
    


<210>  3
<211>  35
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  The n-terminal contains a variable acetyl sequence

<220>
<221>  MISC_FEATURE
<223>  The c-terminal contains an amino group

<400>  3

Leu Ser Glu Leu Asp Asp Arg Ala Asp Ala Leu Gln Ala Gly Ala Ser 
1               5                   10                  15      


Gln Phe Glu Thr Ser Ala Ala Lys Leu Lys Arg Lys Tyr Trp Trp Lys 
            20                  25                  30          


Asn Leu Lys 
        35  


<210>  4
<211>  5
<212>  PRT
<213>  Clostridium botulinum


<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  Xaa can be any naturally occurring amino acid

<400>  4

His Glu Xaa Xaa His 
1               5   


<210>  5
<211>  1275
<212>  DNA
<213>  Clostridium botulinum


<220>
<221>  misc_feature
<223>  The n-terminal contains a variable acetyl sequence

<220>
<221>  misc_feature
<223>  The c-terminal contains an amino group

<400>  5
atgcagttcg ttaacaaaca gttcaactac aaagacccgg ttaacggtgt tgacatcgct       60

tacatcaaaa tcccgaacgt tggtcagatg cagccggtta aagcattcaa aatccacaac      120

aaaatctggg ttatcccgga acgtgacact ttcactaacc cggaagaagg tgacctgaac      180

ccgccgccgg aagctaaaca ggttccggtt tcttactacg actctactta cctgtctact      240

gacaacgaaa aggacaacta cctgaaaggt gttactaaac tgtttgaacg tatctactct      300

actgacctgg gtcgcatgct gctcacttct atcgttcgtg gtatcccgtt ctggggtggt      360

tctactatcg acactgaact gaaagttatc gacactaact gcatcaacgt tatccagccg      420

gacggttctt accgttctga agaactgaac ctggttatca tcggtccgtc tgctgacatc      480

atccagtttg aatgcaaatc tttcggtcac gaagttctga acctgactcg taacggttac      540

ggttctactc agtacatccg tttctctccg gacttcactt tcggtttcga agaatctctg      600

gaagttgaca ctaacccgct gctgggtgct ggtaaattcg ctactgaccc ggctgttact      660

ctggctcacg aactgatcca cgctggtcac cgtctgtacg gtatcgctat caacccgaac      720

cgtgttttca aagttaacac taacgcttac tacgaaatgt ctggtctgga agtttctttt      780

gaagaactgc gtactttcgg tggtcacgac gctaaattca tcgactctct gcaggaaaac      840

gagttccgtc tgtactacta caacaaattc aaagacatcg cttctactct gaacaaagct      900

aaatctatcg ttggtaccac tgcttctctg cagtacatga agaacgtttt caaagaaaag      960

tacctgctgt ctgaagacac ttctggtaaa ttctctgttg acaaactgaa attcgacaaa     1020

ctgtacaaaa tgctgactga aatctacact gaagacaact tcgttaaatt cttcaaagtt     1080

ctgaaccgta aaacttacct gaacttcgac aaagctgttt tcaaaatcaa catcgttccg     1140

aaagttaact acactatcta cgacggtttc aacctgcgta acactaacct ggctgctaac     1200

ttcaacggtc agaacactga aatcaacaac atgaacttca ctaaactgaa gaacttcact     1260

ggtctgtttg agttc                                                      1275


<210>  6
<211>  425
<212>  PRT
<213>  Clostridium botulinum

<400>  6

Met Gln Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly 
1               5                   10                  15      


Val Asp Ile Ala Tyr Ile Lys Ile Pro Asn Val Gly Gln Met Gln Pro 
            20                  25                  30          


Val Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg 
        35                  40                  45              


Asp Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu 
    50                  55                  60                  


Ala Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr 
65                  70                  75                  80  


Asp Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu 
                85                  90                  95      


Arg Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val 
            100                 105                 110         


Arg Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys 
        115                 120                 125             


Val Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr 
    130                 135                 140                 


Arg Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile 
145                 150                 155                 160 


Ile Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr 
                165                 170                 175     


Arg Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe 
            180                 185                 190         


Thr Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu 
        195                 200                 205             


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


Leu Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn 
225                 230                 235                 240 


Arg Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu 
                245                 250                 255     


Glu Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys 
            260                 265                 270         


Phe Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn 
        275                 280                 285             


Lys Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val 
    290                 295                 300                 


Gly Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys 
305                 310                 315                 320 


Tyr Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu 
                325                 330                 335     


Lys Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp 
            340                 345                 350         


Asn Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn 
        355                 360                 365             


Phe Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr 
    370                 375                 380                 


Thr Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn 
385                 390                 395                 400 


Phe Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu 
                405                 410                 415     


Lys Asn Phe Thr Gly Leu Phe Glu Phe 
            420                 425 


<210>  7
<211>  1293
<212>  DNA
<213>  Clostridium botulinum

<400>  7
atgccgaaaa tcaactcgtt caactacaac gacccggtga atgaccgcac aatcctgtac       60

attaagccgg gcggttgcca ggagttctac aagagcttta acattatgaa gaacatctgg      120

atcatccctg aacgcaatgt gatcgggaca acgccacaag atttccaccc tccgacttcg      180

ctcaaaaacg gggactcctc ctactacgac ccaaattact tgcaaagcga tgaggagaaa      240

gatcggttcc tgaagattgt gacaaagatc ttcaaccgta ttaacaacaa tctctcgggg      300

ggcatcctcc tggaggaatt atccaaggcg aacccttacc tgggcaacga caacactcca      360

gacaaccagt tccacattgg cgacgcctcc gcggtggaga tcaagttctc gaatggcagt      420

caggacatcc ttctccctaa tgtcattatt atgggcgccg agccggacct ttttgaaacc      480

aattccagca acatctcgct gcgcaacaac tacatgccga gcaatcacgg ctttgggtcg      540

atcgcgatcg tgactttctc gccggagtac tcctttcgct tcaacgacaa ctccatgaac      600

gagttcattc aggacccggc gctcaccctc atgcacgagc tgatccactc gttacatggc      660

ttgtacggcg cgaaggggat cacgaccaag tataccatta cgcagaaaca gaacccactt      720

atcacgaaca tccgtgggac gaacatcgag gagttcctca cgttcggggg gaccgacctg      780

aacattatca ccagcgccca gtccaacgac atttacacga acctgctggc agattacaaa      840

aaaattgcct ccaagctctc caaggtccag gtatcgaacc cgttgctcaa tccttacaag      900

gacgtcttcg aggctaagta tgggctggat aaggatgcct caggaatcta ctctgtgaac      960

atcaacaaat tcaacgacat cttcaagaag ctgtacagct tcaccgagtt tgacctcgcc     1020

accaagttcc aggtcaaatg tcggcaaacg tacattggcc agtataaata ttttaagctg     1080

tcgaatcttc tcaacgactc tatctataac atctccgagg ggtacaatat taacaactta     1140

aaagtcaact tccgagggca gaacgcaaat ctcaacccac ggattattac tcctattaca     1200

ggccgcgggc tcgtcaagaa gatcatccga ttttgcaaaa acattgtcag cgttaaaggc     1260

atccgtaagc tcgagcacca ccaccaccac cac                                  1293


<210>  8
<211>  431
<212>  PRT
<213>  Clostridium botulinum

<400>  8

Met Pro Lys Ile Asn Ser Phe Asn Tyr Asn Asp Pro Val Asn Asp Arg 
1               5                   10                  15      


Thr Ile Leu Tyr Ile Lys Pro Gly Gly Cys Gln Glu Phe Tyr Lys Ser 
            20                  25                  30          


Phe Asn Ile Met Lys Asn Ile Trp Ile Ile Pro Glu Arg Asn Val Ile 
        35                  40                  45              


Gly Thr Thr Pro Gln Asp Phe His Pro Pro Thr Ser Leu Lys Asn Gly 
    50                  55                  60                  


Asp Ser Ser Tyr Tyr Asp Pro Asn Tyr Leu Gln Ser Asp Glu Glu Lys 
65                  70                  75                  80  


Asp Arg Phe Leu Lys Ile Val Thr Lys Ile Phe Asn Arg Ile Asn Asn 
                85                  90                  95      


Asn Leu Ser Gly Gly Ile Leu Leu Glu Glu Leu Ser Lys Ala Asn Pro 
            100                 105                 110         


Tyr Leu Gly Asn Asp Asn Thr Pro Asp Asn Gln Phe His Ile Gly Asp 
        115                 120                 125             


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


Leu Pro Asn Val Ile Ile Met Gly Ala Glu Pro Asp Leu Phe Glu Thr 
145                 150                 155                 160 


Asn Ser Ser Asn Ile Ser Leu Arg Asn Asn Tyr Met Pro Ser Asn His 
                165                 170                 175     


Gly Phe Gly Ser Ile Ala Ile Val Thr Phe Ser Pro Glu Tyr Ser Phe 
            180                 185                 190         


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


Thr Leu Met His Glu Leu Ile His Ser Leu His Gly Leu Tyr Gly Ala 
    210                 215                 220                 


Lys Gly Ile Thr Thr Lys Tyr Thr Ile Thr Gln Lys Gln Asn Pro Leu 
225                 230                 235                 240 


Ile Thr Asn Ile Arg Gly Thr Asn Ile Glu Glu Phe Leu Thr Phe Gly 
                245                 250                 255     


Gly Thr Asp Leu Asn Ile Ile Thr Ser Ala Gln Ser Asn Asp Ile Tyr 
            260                 265                 270         


Thr Asn Leu Leu Ala Asp Tyr Lys Lys Ile Ala Ser Lys Leu Ser Lys 
        275                 280                 285             


Val Gln Val Ser Asn Pro Leu Leu Asn Pro Tyr Lys Asp Val Phe Glu 
    290                 295                 300                 


Ala Lys Tyr Gly Leu Asp Lys Asp Ala Ser Gly Ile Tyr Ser Val Asn 
305                 310                 315                 320 


Ile Asn Lys Phe Asn Asp Ile Phe Lys Lys Leu Tyr Ser Phe Thr Glu 
                325                 330                 335     


Phe Asp Leu Ala Thr Lys Phe Gln Val Lys Cys Arg Gln Thr Tyr Ile 
            340                 345                 350         


Gly Gln Tyr Lys Tyr Phe Lys Leu Ser Asn Leu Leu Asn Asp Ser Ile 
        355                 360                 365             


Tyr Asn Ile Ser Glu Gly Tyr Asn Ile Asn Asn Leu Lys Val Asn Phe 
    370                 375                 380                 


Arg Gly Gln Asn Ala Asn Leu Asn Pro Arg Ile Ile Thr Pro Ile Thr 
385                 390                 395                 400 


Gly Arg Gly Leu Val Lys Lys Ile Ile Arg Phe Cys Lys Asn Ile Val 
                405                 410                 415     


Ser Val Lys Gly Ile Arg Lys Leu Glu His His His His His His 
            420                 425                 430     


