                               SEQUENCE LISTING	

<110> THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
 
<120> NEURAMINIDASE INHIBITORS AND USES THEREOF

<130> 19240-572.WO2

<140> PCT/US2009/064393
<141> 2009-11-13

<150> 61/114,104
<151> 2008-11-13

<160> 4     

<170> PatentIn version 3.5

<210> 1
<211> 2994
<212> DNA
<213> Streptococcus pneumoniae

<400> 1
atgattgtag gagcagtggt atttggaacg tctcctgttt tagctcaaga aggggcaagt       60

gagcaacctc tggcaaatga aactcaactt tcgggggaga gctcaaccct aactgataca      120

gaaaagagcc agccttcttc agagactgaa ctttctggca ataagcaaga acaagaaagg      180

aaagataagc aagaagaaaa aattccaaga gattactatg cacgagattt ggaaaatgtc      240

gaaacagtga tagaaaaaga agatgttgaa accaatgctt caaatggtca gagagttgat      300

ttatcaagtg aactagataa actaaagaaa cttgaaaacg caacagttca catggagttt      360

aagccagatg ccaaggcccc agcattctat aatctctttt ctgtgtcaag tgctactaaa      420

aaagatgagt acttcactat ggcagtttac aataatactg ctactctaga ggggcgtggt      480

tcggatggga aacagtttta caataattac aacgatgcac ccttaaaagt taaaccaggt      540

cagtggaatt ctgtgacttt cacagttgaa aaaccgacag cagaactacc taaaggccga      600

gtgcgcctct acgtaaacgg ggtattatct cgaacaagtc tgagatctgg caatttcatt      660

aaagatatgc cagatgtaac gcatgtgcaa atcggagcaa ccaagcgtgc caacaatacg      720

gtttgggggt caaatctaca gattcggaat ctcactgtgt ataatcgtgc tttaacacca      780

gaagaggtac aaaaacgtag tcaacttttt aaacgctcag atttagaaaa aaaactacct      840

gaaggagcgg ctttaacaga gaaaacggac atattcgaaa gcgggcgtaa cggtaaacca      900

aataaagatg gaatcaagag ttatcgtatt ccagcacttc tcaagacaga taaaggaact      960

ttgatcgcag gtgcagatga acgccgtctc cattcgagtg actggggtga tatcggtatg     1020

gtcatcagac gtagtgaaga taatggtaaa acttggggtg accgagtaac cattaccaac     1080

ttacgtgaca atccaaaagc ttctgaccca tcgatcggtt caccagtgaa tatcgatatg     1140

gtgttggttc aagatcctga aaccaaacga atcttttcta tctatgacat gttcccagaa     1200

gggaagggaa tctttggaat gtcttcacaa aaagaagaag cctacaaaaa aatcgatgga     1260

aaaacctatc aaatcctcta tcgtgaagga gaaaagggag cttataccat tcgagaaaat     1320

ggtactgtct atacaccaga tggtaaggcg acagactatc gcgttgttgt agatcctgtt     1380

aaaccagcct atagcgacaa gggggatcta tacaagggta accaattact aggcaatatc     1440

tacttcacaa caaacaaaac ttctccattt agaattgcca aggatagcta tctatggatg     1500

tcctacagtg atgacgacgg gaagacatgg tcagcgcctc aagatattac tccgatggtc     1560

aaagccgatt ggatgaaatt cttgggtgta ggtcctggaa caggaattgt acttcggaat     1620

gggcctcaca agggacggat tttgataccg gtttatacga ctaataatgt atctcactta     1680

aatggctcgc aatcttctcg tatcatctat tcagatgatc atggaaaaac ttggcatgct     1740

ggagaagcgg tcaacgataa ccgtcaggta gacggtcaaa agatccactc ttctacgatg     1800

aacaatagac gtgcgcaaaa tacagaatca acggtggtac aactaaacaa tggagatgtt     1860

aaactcttta tgcgtggttt gactggagat cttcaggttg ctacaagtaa agacggagga     1920

gtgacttggg agaaggatat caaacgttat ccacaggtta aagatgtcta tgttcaaatg     1980

tctgctatcc atacgatgca cgaaggaaaa gaatacatca tcctcagtaa tgcaggtgga     2040

ccgaaacgtg aaaatgggat ggtccacttg gcacgtgtcg aagaaaatgg tgagttgact     2100

tggctcaaac acaatccaat tcaaaaagga gagtttgcct ataattcgct ccaagaatta     2160

ggaaatgggg agtatggcat cttgtatgaa catactgaaa aaggacaaaa tgcctatacc     2220

ctatcattta gaaaatttaa ttgggacttt ttgagcaaag atctgatttc tcctaccgaa     2280

gcgaaagtga agcgaactag agagatgggc aaaggagtta ttggcttgga gttcgactca     2340

gaagtattgg tcaacaaggc tccaaccctt caattggcaa atggtaaaac agcacgcttc     2400

atgacccagt atgatacaaa aaccctccta tttacagtgg attcagagga tatgggtcaa     2460

aaagttacag gtttggcaga aggtgcaatt gaaagtatgc ataatttacc agtctctgtg     2520

gcgggcacta agctttcgaa tggaatgaac ggaagtgaag ctgctgttca tgaagtgcca     2580

gaatacacag gcccattagg gacatccggc gaagagccag ctccaacagt cgagaagcca     2640

gaatacacag gcccactagg gacatccggc gaagagccag ccccgacagt cgagaagcca     2700

gaatacacag gcccactagg gacagctggt gaagaagcag ctccaacagt cgagaagcca     2760

gaatttacag ggggagttaa tggtacagag ccagctgttc atgaaatcgc agagtataag     2820

ggatctgatt cgcttgtaac tcttactaca aaagaagatt atacttacaa agctcctctt     2880

gctcagcagg cacttcctga aacaggaaac aaggagagtg acctcctagc ttcactagga     2940

ctaacagctt tcttccttgg tctgtttacg ctagggaaaa agagagaaca ataa           2994


<210> 2
<211> 997
<212> PRT
<213> Streptococcus pneumoniae

<400> 2
Met Ile Val Gly Ala Val Val Phe Gly Thr Ser Pro Val Leu Ala Gln 
1               5                   10                  15      


Glu Gly Ala Ser Glu Gln Pro Leu Ala Asn Glu Thr Gln Leu Ser Gly 
            20                  25                  30          


Glu Ser Ser Thr Leu Thr Asp Thr Glu Lys Ser Gln Pro Ser Ser Glu 
        35                  40                  45              


Thr Glu Leu Ser Gly Asn Lys Gln Glu Gln Glu Arg Lys Asp Lys Gln 
    50                  55                  60                  


Glu Glu Lys Ile Pro Arg Asp Tyr Tyr Ala Arg Asp Leu Glu Asn Val 
65                  70                  75                  80  


Glu Thr Val Ile Glu Lys Glu Asp Val Glu Thr Asn Ala Ser Asn Gly 
                85                  90                  95      


Gln Arg Val Asp Leu Ser Ser Glu Leu Asp Lys Leu Lys Lys Leu Glu 
            100                 105                 110         


Asn Ala Thr Val His Met Glu Phe Lys Pro Asp Ala Lys Ala Pro Ala 
        115                 120                 125             


Phe Tyr Asn Leu Phe Ser Val Ser Ser Ala Thr Lys Lys Asp Glu Tyr 
    130                 135                 140                 


Phe Thr Met Ala Val Tyr Asn Asn Thr Ala Thr Leu Glu Gly Arg Gly 
145                 150                 155                 160 


Ser Asp Gly Lys Gln Phe Tyr Asn Asn Tyr Asn Asp Ala Pro Leu Lys 
                165                 170                 175     


Val Lys Pro Gly Gln Trp Asn Ser Val Thr Phe Thr Val Glu Lys Pro 
            180                 185                 190         


Thr Ala Glu Leu Pro Lys Gly Arg Val Arg Leu Tyr Val Asn Gly Val 
        195                 200                 205             


Leu Ser Arg Thr Ser Leu Arg Ser Gly Asn Phe Ile Lys Asp Met Pro 
    210                 215                 220                 


Asp Val Thr His Val Gln Ile Gly Ala Thr Lys Arg Ala Asn Asn Thr 
225                 230                 235                 240 


Val Trp Gly Ser Asn Leu Gln Ile Arg Asn Leu Thr Val Tyr Asn Arg 
                245                 250                 255     


Ala Leu Thr Pro Glu Glu Val Gln Lys Arg Ser Gln Leu Phe Lys Arg 
            260                 265                 270         


Ser Asp Leu Glu Lys Lys Leu Pro Glu Gly Ala Ala Leu Thr Glu Lys 
        275                 280                 285             


Thr Asp Ile Phe Glu Ser Gly Arg Asn Gly Lys Pro Asn Lys Asp Gly 
    290                 295                 300                 


Ile Lys Ser Tyr Arg Ile Pro Ala Leu Leu Lys Thr Asp Lys Gly Thr 
305                 310                 315                 320 


Leu Ile Ala Gly Ala Asp Glu Arg Arg Leu His Ser Ser Asp Trp Gly 
                325                 330                 335     


Asp Ile Gly Met Val Ile Arg Arg Ser Glu Asp Asn Gly Lys Thr Trp 
            340                 345                 350         


Gly Asp Arg Val Thr Ile Thr Asn Leu Arg Asp Asn Pro Lys Ala Ser 
        355                 360                 365             


Asp Pro Ser Ile Gly Ser Pro Val Asn Ile Asp Met Val Leu Val Gln 
    370                 375                 380                 


Asp Pro Glu Thr Lys Arg Ile Phe Ser Ile Tyr Asp Met Phe Pro Glu 
385                 390                 395                 400 


Gly Lys Gly Ile Phe Gly Met Ser Ser Gln Lys Glu Glu Ala Tyr Lys 
                405                 410                 415     


Lys Ile Asp Gly Lys Thr Tyr Gln Ile Leu Tyr Arg Glu Gly Glu Lys 
            420                 425                 430         


Gly Ala Tyr Thr Ile Arg Glu Asn Gly Thr Val Tyr Thr Pro Asp Gly 
        435                 440                 445             


Lys Ala Thr Asp Tyr Arg Val Val Val Asp Pro Val Lys Pro Ala Tyr 
    450                 455                 460                 


Ser Asp Lys Gly Asp Leu Tyr Lys Gly Asn Gln Leu Leu Gly Asn Ile 
465                 470                 475                 480 


Tyr Phe Thr Thr Asn Lys Thr Ser Pro Phe Arg Ile Ala Lys Asp Ser 
                485                 490                 495     


Tyr Leu Trp Met Ser Tyr Ser Asp Asp Asp Gly Lys Thr Trp Ser Ala 
            500                 505                 510         


Pro Gln Asp Ile Thr Pro Met Val Lys Ala Asp Trp Met Lys Phe Leu 
        515                 520                 525             


Gly Val Gly Pro Gly Thr Gly Ile Val Leu Arg Asn Gly Pro His Lys 
    530                 535                 540                 


Gly Arg Ile Leu Ile Pro Val Tyr Thr Thr Asn Asn Val Ser His Leu 
545                 550                 555                 560 


Asn Gly Ser Gln Ser Ser Arg Ile Ile Tyr Ser Asp Asp His Gly Lys 
                565                 570                 575     


Thr Trp His Ala Gly Glu Ala Val Asn Asp Asn Arg Gln Val Asp Gly 
            580                 585                 590         


Gln Lys Ile His Ser Ser Thr Met Asn Asn Arg Arg Ala Gln Asn Thr 
        595                 600                 605             


Glu Ser Thr Val Val Gln Leu Asn Asn Gly Asp Val Lys Leu Phe Met 
    610                 615                 620                 


Arg Gly Leu Thr Gly Asp Leu Gln Val Ala Thr Ser Lys Asp Gly Gly 
625                 630                 635                 640 


Val Thr Trp Glu Lys Asp Ile Lys Arg Tyr Pro Gln Val Lys Asp Val 
                645                 650                 655     


Tyr Val Gln Met Ser Ala Ile His Thr Met His Glu Gly Lys Glu Tyr 
            660                 665                 670         


Ile Ile Leu Ser Asn Ala Gly Gly Pro Lys Arg Glu Asn Gly Met Val 
        675                 680                 685             


His Leu Ala Arg Val Glu Glu Asn Gly Glu Leu Thr Trp Leu Lys His 
    690                 695                 700                 


Asn Pro Ile Gln Lys Gly Glu Phe Ala Tyr Asn Ser Leu Gln Glu Leu 
705                 710                 715                 720 


Gly Asn Gly Glu Tyr Gly Ile Leu Tyr Glu His Thr Glu Lys Gly Gln 
                725                 730                 735     


Asn Ala Tyr Thr Leu Ser Phe Arg Lys Phe Asn Trp Asp Phe Leu Ser 
            740                 745                 750         


Lys Asp Leu Ile Ser Pro Thr Glu Ala Lys Val Lys Arg Thr Arg Glu 
        755                 760                 765             


Met Gly Lys Gly Val Ile Gly Leu Glu Phe Asp Ser Glu Val Leu Val 
    770                 775                 780                 


Asn Lys Ala Pro Thr Leu Gln Leu Ala Asn Gly Lys Thr Ala Arg Phe 
785                 790                 795                 800 


Met Thr Gln Tyr Asp Thr Lys Thr Leu Leu Phe Thr Val Asp Ser Glu 
                805                 810                 815     


Asp Met Gly Gln Lys Val Thr Gly Leu Ala Glu Gly Ala Ile Glu Ser 
            820                 825                 830         


Met His Asn Leu Pro Val Ser Val Ala Gly Thr Lys Leu Ser Asn Gly 
        835                 840                 845             


Met Asn Gly Ser Glu Ala Ala Val His Glu Val Pro Glu Tyr Thr Gly 
    850                 855                 860                 


Pro Leu Gly Thr Ser Gly Glu Glu Pro Ala Pro Thr Val Glu Lys Pro 
865                 870                 875                 880 


Glu Tyr Thr Gly Pro Leu Gly Thr Ser Gly Glu Glu Pro Ala Pro Thr 
                885                 890                 895     


Val Glu Lys Pro Glu Tyr Thr Gly Pro Leu Gly Thr Ala Gly Glu Glu 
            900                 905                 910         


Ala Ala Pro Thr Val Glu Lys Pro Glu Phe Thr Gly Gly Val Asn Gly 
        915                 920                 925             


Thr Glu Pro Ala Val His Glu Ile Ala Glu Tyr Lys Gly Ser Asp Ser 
    930                 935                 940                 


Leu Val Thr Leu Thr Thr Lys Glu Asp Tyr Thr Tyr Lys Ala Pro Leu 
945                 950                 955                 960 


Ala Gln Gln Ala Leu Pro Glu Thr Gly Asn Lys Glu Ser Asp Leu Leu 
                965                 970                 975     


Ala Ser Leu Gly Leu Thr Ala Phe Phe Leu Gly Leu Phe Thr Leu Gly 
            980                 985                 990         


Lys Lys Arg Glu Gln 
        995         


<210> 3
<211> 470
<212> PRT
<213> Streptococcus pneumoniae

<400> 3
Ala Leu Thr Glu Lys Thr Asp Ile Phe Glu Ser Gly Arg Asn Gly Lys 
1               5                   10                  15      


Pro Asn Lys Asp Gly Ile Lys Ser Tyr Arg Ile Pro Ala Leu Leu Lys 
            20                  25                  30          


Thr Asp Lys Gly Thr Leu Ile Ala Gly Ala Asp Glu Arg Arg Leu His 
        35                  40                  45              


Ser Ser Asp Trp Gly Asp Ile Gly Met Val Ile Arg Arg Ser Glu Asp 
    50                  55                  60                  


Asn Gly Lys Thr Trp Gly Asp Arg Val Thr Ile Thr Asn Leu Arg Asp 
65                  70                  75                  80  


Asn Pro Lys Ala Ser Asp Pro Ser Ile Gly Ser Pro Val Asn Ile Asp 
                85                  90                  95      


Met Val Leu Val Gln Asp Pro Glu Thr Lys Arg Ile Phe Ser Ile Tyr 
            100                 105                 110         


Asp Met Phe Pro Glu Gly Lys Gly Ile Phe Gly Met Ser Ser Gln Lys 
        115                 120                 125             


Glu Glu Ala Tyr Lys Lys Ile Asp Gly Lys Thr Tyr Gln Ile Leu Tyr 
    130                 135                 140                 


Arg Glu Gly Glu Lys Gly Ala Tyr Thr Ile Arg Glu Asn Gly Thr Val 
145                 150                 155                 160 


Tyr Thr Pro Asp Gly Lys Ala Thr Asp Tyr Arg Val Val Val Asp Pro 
                165                 170                 175     


Val Lys Pro Ala Tyr Ser Asp Lys Gly Asp Leu Tyr Lys Gly Asn Gln 
            180                 185                 190         


Leu Leu Gly Asn Ile Tyr Phe Thr Thr Asn Lys Thr Ser Pro Phe Arg 
        195                 200                 205             


Ile Ala Lys Asp Ser Tyr Leu Trp Met Ser Tyr Ser Asp Asp Asp Gly 
    210                 215                 220                 


Lys Thr Trp Ser Ala Pro Gln Asp Ile Thr Pro Met Val Lys Ala Asp 
225                 230                 235                 240 


Trp Met Lys Phe Leu Gly Val Gly Pro Gly Thr Gly Ile Val Leu Arg 
                245                 250                 255     


Asn Gly Pro His Lys Gly Arg Ile Leu Ile Pro Val Tyr Thr Thr Asn 
            260                 265                 270         


Asn Val Ser His Leu Asn Gly Ser Gln Ser Ser Arg Ile Ile Tyr Ser 
        275                 280                 285             


Asp Asp His Gly Lys Thr Trp His Ala Gly Glu Ala Val Asn Asp Asn 
    290                 295                 300                 


Arg Gln Val Asp Gly Gln Lys Ile His Ser Ser Thr Met Asn Asn Arg 
305                 310                 315                 320 


Arg Ala Gln Asn Thr Glu Ser Thr Val Val Gln Leu Asn Asn Gly Asp 
                325                 330                 335     


Val Lys Leu Phe Met Arg Gly Leu Thr Gly Asp Leu Gln Val Ala Thr 
            340                 345                 350         


Ser Lys Asp Gly Gly Val Thr Trp Glu Lys Asp Ile Lys Arg Tyr Pro 
        355                 360                 365             


Gln Val Lys Asp Val Tyr Val Gln Met Ser Ala Ile His Thr Met His 
    370                 375                 380                 


Glu Gly Lys Glu Tyr Ile Ile Leu Ser Asn Ala Gly Gly Pro Lys Arg 
385                 390                 395                 400 


Glu Asn Gly Met Val His Leu Ala Arg Val Glu Glu Asn Gly Glu Leu 
                405                 410                 415     


Thr Trp Leu Lys His Asn Pro Ile Gln Lys Gly Glu Phe Ala Tyr Asn 
            420                 425                 430         


Ser Leu Gln Glu Leu Gly Asn Gly Glu Tyr Gly Ile Leu Tyr Glu His 
        435                 440                 445             


Thr Glu Lys Gly Gln Asn Ala Tyr Thr Leu Ser Phe Arg Lys Phe Asn 
    450                 455                 460                 


Trp Asp Phe Leu Ser Lys 
465                 470 


<210> 4
<211> 470
<212> PRT
<213> Streptococcus pneumoniae

<400> 4
Ala Leu Thr Glu Lys Thr Asp Ile Phe Glu Ser Gly Arg Asn Gly Lys 
1               5                   10                  15      


Pro Asn Lys Asp Gly Ile Lys Ser Tyr Arg Ile Pro Ala Leu Leu Lys 
            20                  25                  30          


Thr Asp Lys Gly Thr Leu Ile Ala Gly Ala Asp Glu Arg Arg Leu His 
        35                  40                  45              


Ser Ser Asp Trp Gly Asp Ile Gly Met Val Ile Arg Arg Ser Glu Asp 
    50                  55                  60                  


Asn Gly Lys Thr Trp Gly Asp Arg Val Thr Ile Thr Asn Leu Arg Asp 
65                  70                  75                  80  


Asn Pro Lys Ala Ser Asp Pro Ser Ile Gly Ser Pro Val Asn Ile Asp 
                85                  90                  95      


Met Val Leu Val Gln Asp Pro Glu Thr Lys Arg Ile Phe Ser Ile Tyr 
            100                 105                 110         


Asp Met Phe Pro Glu Gly Lys Gly Ile Phe Gly Met Ser Ser Gln Lys 
        115                 120                 125             


Glu Glu Ala Tyr Lys Lys Ile Asp Gly Lys Thr Tyr Gln Ile Leu Tyr 
    130                 135                 140                 


Arg Glu Gly Glu Lys Gly Ala Tyr Thr Ile Arg Glu Asn Gly Thr Val 
145                 150                 155                 160 


Tyr Thr Pro Asp Gly Lys Ala Thr Asp Tyr Arg Val Val Val Asp Pro 
                165                 170                 175     


Val Lys Pro Ala Tyr Ser Asp Lys Gly Asp Leu Tyr Lys Gly Asn Gln 
            180                 185                 190         


Leu Leu Gly Asn Ile Tyr Phe Thr Thr Asn Lys Thr Ser Pro Phe Arg 
        195                 200                 205             


Ile Ala Lys Asp Ser Tyr Leu Trp Met Ser Tyr Ser Asp Asp Asp Gly 
    210                 215                 220                 


Lys Thr Trp Ser Ala Pro Gln Asp Ile Thr Pro Met Val Lys Ala Asp 
225                 230                 235                 240 


Trp Met Lys Phe Leu Gly Val Gly Pro Gly Thr Gly Ile Val Leu Arg 
                245                 250                 255     


Asn Gly Pro His Lys Gly Arg Ile Leu Ile Pro Val Tyr Thr Thr Asn 
            260                 265                 270         


Asn Val Ser His Leu Asn Gly Ser Gln Ser Ser Arg Ile Ile Tyr Ser 
        275                 280                 285             


Asp Asp His Gly Lys Thr Trp His Ala Gly Glu Ala Val Asn Asp Asn 
    290                 295                 300                 


Arg Gln Val Asp Gly Gln Lys Ile His Ser Ser Thr Met Asn Asn Arg 
305                 310                 315                 320 


Arg Ala Gln Asn Thr Glu Ser Thr Val Val Gln Leu Asn Asn Gly Asp 
                325                 330                 335     


Val Lys Leu Phe Met Arg Gly Leu Thr Gly Asp Leu Gln Val Ala Thr 
            340                 345                 350         


Ser Lys Asp Gly Gly Val Thr Trp Glu Lys Asp Ile Lys Arg Tyr Pro 
        355                 360                 365             


Gln Val Lys Asp Val Tyr Val Gln Met Ser Ala Ile His Thr Met His 
    370                 375                 380                 


Glu Gly Lys Glu Tyr Ile Ile Leu Ser Asn Ala Gly Gly Pro Lys Arg 
385                 390                 395                 400 


Glu Asn Gly Met Val His Leu Ala Arg Val Glu Glu Asn Gly Glu Leu 
                405                 410                 415     


Thr Trp Leu Lys His Asn Pro Ile Gln Lys Gly Glu Phe Ala Tyr Asn 
            420                 425                 430         


Ser Leu Gln Glu Leu Gly Asn Gly Glu Tyr Gly Ile Leu Tyr Glu His 
        435                 440                 445             


Thr Glu Lys Gly Gln Asn Ala Tyr Thr Leu Ser Phe Arg Lys Phe Asn 
    450                 455                 460                 


Trp Asp Phe Leu Ser Lys 
465                 470 




