(WO202086885) Multivalent glycopeptides that tightly bind to carbohydrate-binding monoclonal antibody family pgt128 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(WO202086885) Multivalent glycopeptides that tightly bind to carbohydrate-binding monoclonal antibody family pgt128
公开号/公开日
WO2020/086885WO2020/086885 / 2020-05-222020-04-30
申请号/申请日
WOUS2019/057921 / 2019-10-24
发明人
KRAUSS ISAACHORIYA SATORUBAILEY JENNIFER;
申请人
BRANDEIS UNIVERSITY;
主分类号
IPC分类号
摘要
(WO2020/086885) The invention relates to a glycopeptide that includes one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopeptide binds specifically to a carbohydrate-binding monoclonal antibody from PGT128 family, preferably with an affinity of less than 100 nM. Immunogenic conjugates that include the glycopeptide, and pharmaceutical compositions that include the glycopeptide or the immunogenic conjugate are also disclosed. Various method of using the glycopeptides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral infection, treating a cancerous condition, and detecting a neutralizing antibody.
机翻摘要
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地址
代理人
(WO202086885) MERKEL, Edwin, V. et al. ([US])
代理机构
;
优先权号
2018US-62750217 2019US-62879372
主权利要求
(WO2020/086885) WHAT IS CLAIMED: 1. A glycopeptide comprising one or more modified amino acid residues having a sidechain comprising an oligosaccharide, wherein the glycopeptide binds specifically to carbohydrate-binding monoclonal antibody PGT128, PGT130, or germline PGT128 with an affinity of less than 100 nM. 2. The glycopeptide according to claim 1, wherein the glycopeptide comprises L amino acids. 3. The glycopeptide according to claim 1, wherein the glycopeptide comprises D amino acids. 4. The glycopeptide according to claim 1, wherein the glycopeptide comprises a mixture of L and D amino acids. 5. The glycopeptide according to any one of claims 1 to 4, wherein the glycopeptide comprises about 10 to about 80 amino acids. 6. The glycopeptide according to any one of claims 1 to 4, wherein the glycopeptide comprises from 1 to about 10 of said modified amino acid residues. 7. The glycopeptide according to claim 6, wherein the glycopeptide comprises from 2 to 5 of said modified amino acid residues. 8. The glycopeptide according to claim 6, wherein two or more of said amino acid residues are at nonadjacent positions in the glycopeptide. 9. The glycopeptide according to claim 6, wherein two or more of said amino acid residues are at adjacent positions in the glycopeptide. 10. The glycopeptide according to any one of claims 1 to 4, wherein the glycopeptide contains one of said modified amino acid residues. 11. The glycopeptide according to any one of claims 1 to 10, wherein the   oligosaccharide is a branched oligosaccharide. 12. The glycopeptide according to claim 11, wherein the branched oligosaccharide consists of 9 mannose moieties and 2 N-Acetylglucosamine moieties. 13. The glycopeptide according to any one of claims 1 to 12, wherein modified amino acid comprises a linker molecule between the polypeptide chain and the monosaccharide or   N - N oligosaccharide, the linker molecule comprisingor   wherein each of Ri and R2 is optionally a direct link or independently selected from the group consisting of a linear or branched Ci to Cl8 hydrocarbon that is saturated or mono- or poly-unsaturated, optionally interrupted by one or more non-adjacent -0-, -C(=0)-, or -NR4-; a substituted or unsubstituted C3 to Cl0 cycloalkanediyl, a substituted or unsubstituted aryl diradical; a substituted or unsubstituted heteroaryl diradical; a monosaccharide diradical; or a disaccharide diradical;   R3 is optional and can be -0-, -S-, or -NR4-; and   Rt is H or a Ci to Cl0 alkyl. 14. The glycopeptide according to any one of claims 1 to 13, wherein the   glycopeptide binds specifically to monoclonal antibody PGT128 with an affinity of less than 50 nM. 15. The glycopeptide according to any one of claims 1 to 13, wherein the   glycopeptide binds specifically to monoclonal antibody PGT128 with an affinity of less than 10 nM. 16. The glycopeptide according to claim 1, wherein the monoclonal antibody PGT128 binds specifically to Man9GlcNAc2 glycans on HIV gpl20 with an affinity comparable to the affinity of PGT128 binding to said glycopeptide. 17. The glycopeptide according to claim 1, wherein the glycopeptide binds specifically to PGT128 and comprises the sequence IGDIR (SEQ ID NO: 1) or IGDIRxA (SEQ ID NO:2), and a modified amino acid residue to which the oligosaccharide is linked. 18. The glycopeptide according to claim 17, wherein said glycopeptide comprises the sequence:   Sequence _ SEQ ID NO:   MAYFVHKKSRLLTNKAVKKRLHGCFQNQRSTIGDIRYAKCXRVSSNFFRRGS 8  VSLGHHHHHHRL  MASHINSNPNQLLLLYLKSTIGDIRCAXCXDFRHYRNTKYVFXTRHNRRTGY 9  GSLGHHHHHHRL  MASYYIHDIAVSAYSKRRGYHNIQVESLYPKIGDIRSAKCXTWRNHRHTXGS 10  GSLGHHHHHHRL  MAHYSXNHXRHPLYPSVNHRXSYPRIGLLSRIGDIRSASCXLRCFRXRSTGS 11  GSLGHHHHHHRL  MAHNLRTXRNKNLIXLAFLHAPILKSRRLVHIGDIRVAACTHXVDVAPXYGS 12  GSLGHHHHHHRL  XYPNTLNNVYQKCNKYNVIGDIRXARCXHXEHFSSQDQPKSKHKRRYKGFGS 13  LGHHHHHHRL  MALIHSRQLVYSKNYXCCLDIGDIRHVLRGKYNDHLFGNAIYRKGVKAFNGS 14  GSLGHHHHHHRL  MADNEFKILXIAXLHKSKHRTYLDYLNLVWXIGDIRAFQXXLKTVLXEAKGS 15  GSLGHHHHHHRL  MAFHHXPHFTXRLPLLRRNCIGDIRRLYSPLPRDPHANFKFSFVEPNANRGS 16  GSLGHHHHHHGYR  MATDHNHSHRRPRREHLDXNXHYSRPXVANXIGDIRTFRRRYIQVXYHLXGS 17  DSLGHHHHHHRL  MAHXS I PHHRKS IDDSLRHLIGDIRYRNRYLXRILYRTSHYKNYYCQHS IGS 18  GSLGHHHHHHRL  MANLXXYKXWNXTLFQWXATHRYSHFHNKCIGDIRTTXSWTRSXXXHAXGS 19  GSLGHHHHHHRL  MATFSRYHTIGDIRHHTLKHHQSKGLQXRLI FLKRQFKAXGNCLRWKILFGS 20  CSLGHHHHHHRL  MALNSNSCHXRVATPISSWKIGDIRARFVSYLHYTNFSFSXXKXKFFTKXGS 21  GSLGHHHHHHRL  MANVFPQTDRSLERSQCLFEAFHS IVXHXES IGDIRLECLRITIVALRTTGS 22  GSLGHHHHHHRL  MAIPNGYRAFNRADXLLLTRIGDIRNAHCXARCNYIYELRPLHHYRWSNRGS 23  GSLGHHHHHHRL  MANTFSYHQKLKXGRHTDEILHTHXXHKKXXIGDIRYATCXKCVIKSHFXGS 24  GSLGHHHHHHRL  MAIHKHLHIHNKKFSTFKS I IGDIRLAWCXNEYNIXPRCNSPRRFSYTAFGS 25  GSLGHHHHHHRL  MAFKTNHTRCDHNSQHIVSQFQKPHLKRSRLIGDIRXAICXIKKHRXCHHGS 26  GSLGHHHHHHRL  MAKISRRYHTFRRVLFRKRQIGDIRNAICXVLHHAVXYXQSKNNCKSXVXGS 27  GSLGHHHHHHRL  MAFRLSYHNSFNGPVHRPHVFVHNXYRKGLRIGDIRFAPCXTHHLNSWSHGS 28  GSLGHHHHHHRL  MAHWHRHHGHXIHYPYRFINLLFSPHXLDWIGDIRKANCXWFLYSVAXIGS 29  GSLGHHHHHHRL  MAHFDPYCRLYVPAYNSHTIYYHQKTAYYYLFIGDIRIDAVAENRSPYPLRG 30  SGHHHHHHRLMAFDHHHXLIGDIRNDHNDFYHVEDGFANVYI ILYI IYSQTTSEVLIVSVGS 31  GSLGHHHHHHRL  MAIXFAPRHIGDIRHPKQRTAHWKIKTAYPLKSLWKIRYRLKHIDRI FLSGS 32  GSLGHHHHHHRL  MANXTLLQLKALRXSLSPLFLRLPLKASHAS IGDIRIXKTRRGPSFIRWYGS 33  GSLGHHHHHHRL  MAKFAICHTIGDIRFEFTI IYTPHKYLVXDHDRHVXSLSVXLXSLXNHSRGS 34  GSLGHHHHHHRL  MAKLKDKLNNXKXNTTNASAIGDIRIHANXLDVFLRNXHHKXTNYGRFLXGS 35  GSLGHHHHHHRL  XPHYYHYNTXHXYYRHXHHS IGDIRSHFXPTKHIWLSGXLXLIHYKSSNNGS 36  GSLGHHHHHHRL  MAHYTNNTLRPLARHHHFRLEQRFGRHLTSNIGDIRLNHVFHXXLRRYYVGS 37  GSLGHHHHHHRL  MAKFHDKNSYKSKHKKYNXLIGDIRXFNSYHRXXNCNKLCHPXISWDLFIGS 38  GSLGHHHHHHRL  MAYTEKHNGIGDIRPAICXNSKNQNHRCNHYQIKLYIHXLXRLPHNYR 39  NSGSGSGLGHHHHHHRL  MALTLRYLKI GDIRLANCXTVFPHFLSKKFFENGHRNLARPCT FRRNR 40  HLGSGSGLGHHHHHHRL  MAYHKHRVXHHHEDKATSLTSNLVRLRLKTRIGDIRRALCXLSKFRYL 41  INGSGSGLGHHHHHHRL  MALLHHLRXIGDIRPAHCXVSHQRRYVP I SRKNVFFKRGFNSHPLRKI 42  LWGSGSGLGHHHHHHRL  MARFRHSNNYYLTPFLTPLKTLI SLQLRYRLIGDIRNASYXHKFSNRN 43  RFGSGSGLGHHHHHHRL  MAI FNQGYRIKAWNDLKDIAIGDIRHALCXLVLARIKLQRRXVKYKHD 44  HRGSGSGLGHHHHHHRL  MAHQHHHPNYALXQRRLS IAIGDIRLAI CXFAHLYHCYRKHLXANT I P 45  XKGSGSGLGHHHHHHRL  MAFVTYQHXSQKNFRRYQILRNHFHPQNYRFIGDIRHALCXFI FKNLX 46  RHGSGSGLGHHHHHHRL  MAAXKIRSKIGDIRTAVCXFXHRHHHHHILDPYYLKXIVXYYSLKSRI 47  TLGSGSGLGHHHHHHRL  MAFIKPCXXYLLPPTXLNLYIGDIRRAKCXEAXNNFHXNNKPLXATXP 48  PHGSGSGLGHHHHHHRL  MAKDILKLRIPFATLSGHRNIGDIRHAYCXSLKRPYIQVYSYLNHLKV 49  RFGSGSGLGHHHHHHRL  MATLHNIHDLNHYYRNLNTRI GDIRHATCXYFFXKLKLLKHNRFXDRA 50  IYGSGSGLGHHHHHHRL  MAPYRINQQXNFPWS SALFQIGDIRHARCXDSCRRFTNIXRYVYLKRR 51  XNGSGSGLGHHHHHHRL  MALFKPYPKI GDIRKARCXLQHTLHHRTNKQPSYRRRLKTL I PLFRRC 52  XLGSGSGLGHHHHHHRL  MATNHLHRT I GDIRHAQCX IYL IYLVQNDQYKRNNRT FRLXLNPKLLK 53  RFGSGSGLGHHHHHHRL  MATNSYYHHNPLXRRTHVVXTLKPXNFWAKXIGDIRRAHCXTT INXLK 54  RRGSGSGLGHHHHHHRL  MAILLHVS TRSRYPHHHXAI IGDIRCASCXYPVLKWFYNFNRLKTYRK 55  QFGSGSGLGHHHHHHRL  MAYRTHKLLHHHNDKWKSNI FPRI FVCHYYL I GDIRHARCX I PLE I LR 56  RYGSGSGLGHHHHHHRLMAYSKHRFS FRHNNXLRDRKL IRKFSYHNHS I GDIRVANKFRYLHVFK 57  FI GSGSGLGHHHHHHRL  MAS IKLINQXXTTNPHLRLHIGDIRRLIKDLYXFRVYYRPTNSGRRLF 58  VNGSGSGLGHHHHHHRL  MAHSHHHS PX IE FHSNGRLHI GDIRKFYADALXVLFFKXAFI DRI PFH 59  DAGSGSGLGHHHHHHRL  MANI YFCSRRTNFHNSCYLXIGDIRGLS I YHHIXIHNKLHLLIXYNLL 60  XXGSGSGLGHHHHHHRL  MAIHYHHP I IGDIRLKHNXINAHTKHVPQKLYLDIKFRRLFGLYI LRX 61  LNGSGSGLGHHHHHHRL  MAI LYHYHNI GDIRRSQRHLNXQXRLYVS TLLHS SHTLRRAS I THRIR 62  KFGSGSGLGHHHHHHRL  MAT FSRYHT I GDIRHHTLKHHQSKGLQXRL I FLKRQFKAXGNCLRWKI 63  LFGSGSGLGHHHHHHRL  MAKYTHIHS IGDIRNTYRNKHKHXALNKTNWALFQQHHRXLIRLFYRR 64  LLGSGSGLGHHHHHHRL  MALNKHKHLRNHTRHHSVPT I GDIRKRI HNLLHYLAGFRFFNQXHSKX 65  GVGSGSGLGHHHHHHRL  MAYLHNHHNYSSNNKLHHLEIGDIRLI YQKYLRNPXFXTFLSRKHXNW 66  QRGSGSGLGHHHHHHRL  MANLTAXSRI GDIRKHHFGRPLYLTKHGAYPRYHTRYKHLLTYRHHFP 67  L I GSGSGLGHHHHHHRL  MAKHTHLRPXNFTQRLRKAHIGDIRLPRNI STSRIRTHIKFHLIRXHL 68  RNGSGSGLGHHHHHHRL  MAFLLNHKRI GDIRKLPPLNLXATKTLTKERIRKIVNGFVQRLKGHSW 69  W I GSGSGLGHHHHHHRL  MAIHHSYRGFTLRI PLTTNKIGDIRTAFPYPXLSHLFDRRRWKRGLHN 70   WFGSGSGLGHHHHHHRL_   wherein X is the modified amino acid residue to which the oligosaccharide is linked. 19. The glycopeptide according to claim 17, wherein said glycopeptide comprises the sequence:   Sequence SEQ ID  _ NO:   MAYFVHKKSRLLTNKAVKKRLHGCFQNQRSTIGDIRYAKCXRVSSNFFRRGSV 71  MASHINSNPNQLLLLYLKSTIGDIRCAXCXDFRHYRNTKYVFXTRHNRRTGY 72  MASYYIHDIAVSAYSKRRGYHNIQVESLYPKIGDIRSAKCXTWRNHRHTX 73  MAHYSXNHXRHPLYPSVNHRXSYPRIGLLSRIGDIRSASCXLRCFRXRST 74  MAHNLRTXRNKNLIXLAFLHAPILKSRRLVHIGDIRVAACTHXVDVAPXY 75  XYPNTLNNVYQKCNKYNVIGDIRXARCXHXEHFSSQDQPKSKHKRRYKGF 76  MALIHSRQLVYSKNYXCCLDIGDIRHVLRGKYNDHLFGNAIYRKGVKAFN 77  MADNEFKILXIAXLHKSKHRTYLDYLNLVWXIGDIRAFQXXLKTVLXEAK 78  MAFHHXPHFTXRLPLLRRNCIGDIRRLYSPLPRDPHANFKFSFVEPNANR 79  MATDHNHSHRRPRREHLDXNXHYSRPXVANXIGDIRTFRRRYIQVXYHLXGSD 80  MAHXS I PHHRKS IDDSLRHLIGDIRYRNRYLXRILYRTSHYKNYYCQHS I 81  MANLXXYKXWNXTLFQWXATHRYSHFHNKCIGDIRTTXSWTRSXXXHAX 82  MATFSRYHT IGDIRHHTLKHHQSKGLQXRLI FLKRQFKAXGNCLRWKILFGSC 83  MALNSNSCHXRVATPISSWKIGDIRARFVSYLHYTNFSFSXXKXKFFTKX 84  MANVFPQTDRSLERSQCLFEAFHS IVXHXES IGDIRLECLRITIVALRTT 85MAIPNGYRAFNRADXLLLTRIGDIRNAHCXARCNYIYELRPLHHYRWSNR 86 MANTFSYHQKLKXGRHTDEILHTHXXHKKXXIGDIRYATCXKCVIKSHFX 87 MAIHKHLHIHNKKFSTFKSI IGDIRLAWCXNEYNIXPRCNSPRRFSYTAF 88 MAFKTNHTRCDHNSQHIVSQFQKPHLKRSRLIGDIRXAICXIKKHRXCHH 89 MAKISRRYHTFRRVLFRKRQIGDIRNAICXVLHHAVXYXQSKNNCKSXVX 90 MAFRLSYHNSFNGPVHRPHVFVHNXYRKGLRIGDIRFAPCXTHHLNSWSH 91 MAHWHRHHGHXIHYPYRFINLLFSPHXLDWIGDIRKANCXWFLYSVAXI 92 MAHFDPYCRLYVPAYNSHTIYYHQKTAYYYLFIGDIRIDAVAENRSPYPLRGS 93 MAFDHHHXLIGDIRNDHNDFYHVEDGFANVYI ILYI IYSQTTSEVLIVSV 94 MAIXFAPRHIGDIRHPKQRTAHWKIKTAYPLKSLWKIRYRLKHIDRIFLS 95 MANXTLLQLKALRXSLSPLFLRLPLKASHASIGDIRIXKTRRGPSFIRWY 96 MAKFAICHTIGDIRFEFTI IYTPHKYLVXDHDRHVXSLSVXLXSLXNHSR 97 MAKLKDKLNNXKXNTTNASAIGDIRIHANXLDVFLRNXHHKXTNYGRFLX 98 XPHYYHYNTXHXYYRHXHHSIGDIRSHFXPTKHIWLSGXLXLIHYKSSNN 99 MAHYTNNTLRPLARHHHFRLEQRFGRHLTSNIGDIRLNHVFHXXLRRYYV 100 MAKFHDKNSYKSKHKKYNXLIGDIRXFNSYHRXXNCNKLCHPXISWDLFI 101 MAYTEKHNGIGDIRPAICXNSKNQNHRCNHYQIKLYIHXLXRLPHNYRNS 102 MALTLRYLKIGDIRLANCXTVFPHFLSKKFFENGHRNLARPCT FRRNRHL 103 MAYHKHRVXHHHEDKATSLTSNLVRLRLKTRIGDIRRALCXLSKFRYLIN 104 MALLHHLRXIGDIRPAHCXVSHQRRYVPI SRKNVFFKRGFNSHPLRKILW 105 MARFRHSNNYYLTPFLTPLKTLI SLQLRYRLIGDIRNASYXHKFSNRNRF 106 MAI FNQGYRIKAWNDLKDIAIGDIRHALCXLVLARIKLQRRXVKYKHDHR 107 MAHQHHHPNYALXQRRLS IAIGDIRLAICXFAHLYHCYRKHLXANT I PXK 108 MAFVTYQHXSQKNFRRYQILRNHFHPQNYRFIGDIRHALCXFI FKNLXRH 109 MAAXKIRSKIGDIRTAVCXFXHRHHHHHILDPYYLKXIVXYYSLKSRITL 110 MAFIKPCXXYLLPPTXLNLYIGDIRRAKCXEAXNNFHXNNKPLXATXPPH 111 MAKDILKLRIPFATLSGHRNIGDIRHAYCXSLKRPYIQVYSYLNHLKVRF 112 MATLHNIHDLNHYYRNLNTRIGDIRHATCXYFFXKLKLLKHNRFXDRAIY 113 MAPYRINQQXNFPWSSALFQIGDIRHARCXDSCRRFTNIXRYVYLKRRXN 114 MALFKPYPKIGDIRKARCXLQHTLHHRTNKQPSYRRRLKTLI PLFRRCXL 115 MATNHLHRT IGDIRHAQCXIYLIYLVQNDQYKRNNRTFRLXLNPKLLKRF 116 MATNSYYHHNPLXRRTHVVXTLKPXNFWAKXIGDIRRAHCXTT INXLKRR 117 MAILLHVSTRSRYPHHHXAI IGDIRCASCXYPVLKWFYNFNRLKTYRKQF 118 MAYRTHKLLHHHNDKWKSNI FPRI FVCHYYLIGDIRHARCXI PLE ILRRY 119 MAYSKHRFS FRHNNXLRDRKLIRKFSYHNHS IGDIRVANKFRYLHVFKFI 120 MAS IKLINQXXTTNPHLRLHIGDIRRLIKDLYXFRVYYRPTNSGRRLFVN 121 MAHSHHHSPXIEFHSNGRLHIGDIRKFYADALXVLFFKXAFIDRIPFHDA 122 MANIYFCSRRTNFHNSCYLXIGDIRGLS IYHHIXIHNKLHLLIXYNLLXX 123 MAIHYHHPI IGDIRLKHNXINAHTKHVPQKLYLDIKFRRLFGLYILRXLN 124 MAILYHYHNIGDIRRSQRHLNXQXRLYVSTLLHSSHTLRRAS I THRIRKF 125 MATFSRYHT IGDIRHHTLKHHQSKGLQXRL I FLKRQFKAXGNCLRWKILF 126 MAKYTHIHS IGDIRNTYRNKHKHXALNKTNWALFQQHHRXLIRLFYRRLL 127 MALNKHKHLRNHTRHHSVPT IGDIRKRIHNLLHYLAGFRFFNQXHSKXGV 128 MAYLHNHHNYSSNNKLHHLE IGDIRLIYQKYLRNPXFXTFLSRKHXNWQR 129 MANLTAXSRIGDIRKHHFGRPLYLTKHGAYPRYHTRYKHLLTYRHHFPLI 130 MAKHTHLRPXNFTQRLRKAHIGDIRLPRNI STSRIRTHIKFHL IRXHLRN 131 MAFLLNHKRIGDIRKLPPLNLXATKTLTKERIRKIVNGFVQRLKGHSWWI 132 MAIHHSYRGFTLRI PLTTNKIGDIRTAFPYPXLSHLFDRRRWKRGLHNWF 133 wherein X is the modified amino acid residue to which the oligosaccharide is linked. 20. The glycopeptide according to claim 1, wherein the glycopeptide comprises a modified amino acid residue to which the oligosaccharide is linked. 21. The glycopeptide according to claim 20, wherein the glycopeptide comprises the sequence:   Sequence _ SEQ ID NO:   MAYFQNTSINNINALNQATQKNFFRIRLEIXTLNLVSKRYCNAXXHLLXXGFGS 134  LGHHHHHHRL  MARFHSRSPFKDSHLFRNGTVGDIRSRAVHAQAEQRRGYLLVRLRGHRVGGLGS 135  LGHHHHHHRL  MAKLKVCNXYAFSRPGWXIRKDIEFYYRINLVGDVRYATCXRYGYLILTQGSGS 136  LGHHHHHHRL  MATYHXTINXNXAYRXRTYSARNSIVSTENHIDDIRAAQCXTNPKHLSFIGSGT 137  LGHHHHHHRL  MANHKHTHISLKSIVQTHGGPHPNVARAANLLLEQLPVVRRRLQRRLLQRGLRS 138  LGHHHHHHRL  XSNYVNSYLNTHLQLDQSTTIGDIHGLRKLGRYATESSFXRIHNISFLSHGSGS 139  LGHHHHHHRL  MAIRKNFPXTFGHRPHLRVAHAQRAQHALLVLRRARRLLDQEVDAPGGRRG 140  SGSGLGHHHHHHRL  MAHHYPNYHXRSHGDRLTLLRHLXS FLVDHKQILXFLLRXRKNHVSXXXTG 141  SGSGLGHHHHHHRL   wherein X is the modified amino acid residue to which the oligosaccharide is linked. 22. The glycopeptide according to claim 20, wherein the glycopeptide comprises the sequence:   Sequence SEQ ID  _ NO:   MAYFQNTSINNINALNQATQKNFFRIRLEIXTLNLVSKRYCNAXXHLLXXGF 142  MARFHSRSPFKDSHLFRNGTVGDIRSRAVHAQAEQRRGYLLVRLRGHRVGGL 143  MAKLKVCNXYAFSRPGWXIRKDIEFYYRINLVGDVRYATCXRYGYLILTQ 144  MATYHXTINXNXAYRXRTYSARNSIVSTENHIDDIRAAQCXTNPKHLSFIGSGT 145  MANHKHTHISLKSIVQTHGGPHPNVARAANLLLEQLPWRRRLQRRLLQRGLR 146  XSNYVNSYLNTHLQLDQSTTIGDIHGLRKLGRYATESSFXRIHNISFLSH 147  MAIRKNFPXTFGHRPHLRVAHAQRAQHALLVLRRARRLLDQEVDAPGGRR 148  MAHHYPNYHXRSHGDRLTLLRHLXS FLVDHKQILXFLLRXRKNHVSXXXT 149 wherein X is the modified amino acid residue to which the oligosaccharide is linked. 23. The glycopeptide according to claim 1, wherein the glycopeptide is a cyclic glycopeptide. 24. The glycopeptide according to claim 23, wherein the glycopeptide comprises the sequence:   SEQ ID   Sequence _ NO:   |- linker - 1 8  MAYFVHKKSRLLTNKAVKKRLHGCFQNQRSTIGDIRYAKCXRVSSNFFRRGSVSL  GHHHHHHRL   [-linker—| 9  MASHINSNPNQLLLLYLKSTIGDIRCAX_ CXDFRHYRNTKYVFXTRHNRRT   GYGSLGHHHHHHRL   [Linker—| 11  MAHYSXNHXRHPLYPSVNHRXSYPRIGLLSRIGDIRSASCXLR_CFRXRSTG   SGSLGHHHHHHRL   I- Linker- 13  XYPNTLNNVYQKCNKYNVIGDIRXARCXHXEHFSSQDQPKSKHKRRYKGFGSLGH  HHHHHRL   |— linker-] 14  MALIHSRQLVYSKNYXC_ CLDIGDIRHVLRGKYNDHLFGNAIYRKGVKA   FNGSGSLGHHHHHHRL   I—linker- 20  MATFSRYHTIGDIRHHTLKHHQSKGLQXRLIFLKRQFKAXGNCLRWKILFGSCSL GHHHHHHRL   I- linker- 22  MANVFPQTDRSLERSQCLFEAFHSIVXHXESIGDIRLECLRITIVALRTTGSGSL GHHHHHHRL   [-linker-] 23  MAIPNGYRAFNRADXLLLTRIGDIRNAHCXAR_CNYIYELRPLHHYRWSNRGS   GSLGHHHHHHRL   |-linker-| 24  MANTFSYHQKLKXGRHTDEILHTHXXHKKXXIGDIRYATCXK_CVIKSHFXG   SGSLGHHHHHHRL   I—linker- 25  MAIHKHLHIHNKKFSTFKSI IGDIRLAWCXNEYNIXPRCNSPRRFSYTAFGSGSL GHHHHHHRL   I- linker- 27  MAKISRRYHTFRRVLFRKRQIGDIRNAICXVLHHAVXYXQSKNNCKSXVXGSGSL  GHHHHHHRL   I- linker- 136  MAKLKVCNXYAFSRPGWXIRKDIEFYYRINLVGDVRYATCXRYGYLILTQGSGSL  GHHHHHHRL   [-linker-] 38  MAKFHDKNSYKSKHKKYNXLIGDIRXFNSYHRXXNCNKL_CHPXISWDLFIGS   GSLGHHHHHHRL   I- linker- 71  MAYFVHKKSRLLTNKAVKKRLHGCFQNQRSTIGDIRYAKCXRVSSNFFRRGSV   [-linker-] 72  MASHINSNPNQLLLLYLKSTIGDIRCAX_CXDFRHYRNTKYVFXTRHNRRTG   Y   I—linker-] 74  MAHYSXNHXRHPLYPSVNHRXSYPRIGLLSRIGDIRSASCXLR CFRXRSTI--linker-1 76  XYPNTLNNVYQKCNKYNVIGDIRXARCXHXEHFSSQDQPKSKHKRRYKGF   |—linker-) 77  MALIHSRQLVYSKNYXC_ CLDIGDIRHVLRGKYNDHLFGNAIYRKGVKA   FN   I-linker—| 83  MATFSRYHTIGDIRHHTLKHHQSKGLQXRLIFLKRQFKAXGNCLRWKILFGSC   I- linker- 1 85  MANVFPQTDRSLERSQCLFEAFHSIVXHXESIGDIRLECLRITIVALRTT   [-linker-) 86  MAIPNGYRAFNRADXLLLTRIGDIRNAHCXAR CNYIYELRPLHHYRWSNR   linker-| 87 XK_CVIKSHFX88  MAIHKHLHIHNKKFSTFKSIIGDIRLAWCXNEYNIXPRCNSPRRFSYTAF   I- linker- 1 90  MAKISRRYHTFRRVLFRKRQIGDIRNAICXVLHHAVXYXQSKNNCKSXVX   (-linker-) 101  MAKFHDKNSYKSKHKKYNXLIGDIRXFNSYHRXXNCNKL_CHPXISWDLFI   I- linker- 1 144  MAKLKVCNXYAFSRPGWXIRKDIEFYYRINLVGDVRYATCXRYGYLILTQ   I—linker-1 39  MAYTEKHNGIGDIRPAICXNSKNQNHRCNHYQIKLYIHXLXRLPHNYRNSGSGSG  LGHHHHHHRL   I—linker- 1 40  MALTLRYLKIGDIRLANCXTVFPHFLSKKFFENGHRNLARPCTFRRNRHLGSGSG  LGHHHHHHRL   [-linker—| 45  MAHQHHHPNYALXQRRLSIAIGDIRLAICXFAHLYHCYRKHLXANTIPXKGSGSG LGHHHHHHRL   I- -linker- 1 48  MAFIKPCXXYLLPPTXLNLYIGDIRRAKCXEAXNNFHXNNKPLXATXPPHGSGSG  LGHHHHHHRL   [—linker—| 51  MAPYRINQQXNFPWSSALFQIGDIRHARCXDS_ CRRFTNIXRYVYLKRRXN   GSGSGLGHHHHHHRL   I- linker- 1 52  MALFKPYPKIGDIRKARCXLQHTLHHRTNKQPSYRRRLKTLIPLFRRCXLGSGSG  LGHHHHHHRL   I—linker—| 55  MAILLHVSTRSRYPHHHXAI IGDIRCAS_ CXYPVLKWFYNFNRLKTYRKQ   FGSGSGLGHHHHHHRL   |— linker- 1 56  MAYRTHKLLHHHNDKWKSNIFPRIFVCHYYLIGDIRHARCXIPLEILRRYGSGSG LGHHHHHHRL   [—linker—| 60  MANIYFCSRRTNFHNSCYLXIGDIRGLSIYHHIXIHNKLHLLIXYNLLXXGSGSG LGHHHHHHRL   [—linker-1 102  MAYTEKHNGIGDIRPAICXNSKNQNHRCNHYQIKLYIHXLXRLPHNYRNS   |— linker- 1 103  MALTLRYLKIGDIRLANCXTVFPHFLSKKFFENGHRNLARPCTFRRNRHLI—linker-] 108  MAHQHHHPNYALXQRRLSIAIGDIRLAICXFAHLYHCYRKHLXANTIPXK   I-linker- 111  MAFIKPCXXYLLPPTXLNLYIGDIRRAKCXEAXNNFHXNNKPLXATXPPH   I—linker—| 114  MAPYRINQQXNFPWSSALFQIGDIRHARCXDS_ CRRFTNIXRYVYLKRRX   N  [—linker- 115  MALFKPYPKIGDIRKARCXLQHTLHHRTNKQPSYRRRLKTLIPLFRRCXL   [—linker—| 118  MAILLHVSTRSRYPHHHXAI IGDIRCAS_ CXYPVLKWFYNFNRLKTYRKQ   F   I—linker- 119  MAYRTHKLLHHHNDKWKSNIFPRIFVCHYYLIGDIRHARCXIPLEILRRY   I—linker- 123  MANIYFCSRRTNFHNSCYLXIGDIRGLSIYHHIXIHNKLHLLIXYNLLXX   wherein X is the modified amino acid residue to which the oligosaccharide is linked, and the Cys-Cys linker is a bis-alkylbenzene group or bis-alkylpyridine group. 25. The glycopeptide according to any one of claims 1 to 13, wherein the glycopeptide binds specifically to monoclonal antibody PGT130 with an affinity of less than 50 nM. 26. The glycopeptide according to any one of claims 1 to 13, wherein the glycopeptide binds specifically to monoclonal antibody PGT130 with an affinity of less than 10 nM. 27. The glycopeptide according to claim 1, wherein the monoclonal antibody PGT130 binds specifically to Man9GlcNAc2 glycans on HIV gpl20 with an affinity comparable to the affinity of PGT130 binding to said glycopeptide. 28. The glycopeptide according to claim 1, wherein the glycopeptide binds specifically to PGT130 and comprises the sequence IGDIR (SEQ ID NO: 1) or IGDIRxA (SEQ ID NO:2), and a modified amino acid residue to which the oligosaccharide is linked. 29. The glycopeptide according to claim 28, wherein said glycopeptide comprises the sequence:   Sequence _ SEQ ID NO:  MANHSHGHNIGDIRDATCXLSNCYHYNNRRKNRFTLFTLLRILVQKSLFRGSGS   150  GLGHHHHHHRL  MAI FNQGYRIKAWNDLKDIAIGDIRHALCXLVLARIKLQRRXVKYKHDHRGSGS   151 GLGHHHHHHRL  MAIHHTHLNIGDIRFRHFPRRYRNNWXNFLFLVLRALTWKNRLAFFSNDHGSGS   152  GLGHHHHHHRL  MAINXS IRLIGDIRPAQAQRGHLAPHARRVRHEVLGLVLERLLVLRRLVRGSGS   153 GLGHHHHHHRL  MAFLLNHKRIGDIRKLPPLNLXATKTLTKERIRKIVNGFVQRLKGHSWWIGSGS   154  GLGHHHHHHRL   wherein X is the modified amino acid residue to which the oligosaccharide is linked. 30. The glycopeptide according to claim 28, wherein said glycopeptide comprises the sequence:   Sequence _ SEQ ID NO:   MANHSHGHNIGDIRDATCXLSNCYHYNNRRKNRFTLFTLLRILVQKSLFR 155  MAI FNQGYRIKAWNDLKDIAIGDIRHALCXLVLARIKLQRRXVKYKHDHR 156  MAIHHTHLNIGDIRFRHFPRRYRNNWXNFLFLVLRALTWKNRLAFFSNDH 157  MAINXS IRLIGDIRPAQAQRGHLAPHARRVRHEVLGLVLERLLVLRRLVR 158  MAFLLNHKRIGDIRKLPPLNLXATKTLTKERIRKIVNGFVQRLKGHSWWI 159 wherein X is the modified amino acid residue to which the oligosaccharide is linked. 31. The glycopeptide according to claim 1, wherein the glycopeptide comprises a modified amino acid residue to which the oligosaccharide is linked. 32. The glycopeptide according to claim 31, wherein the glycopeptide comprises the sequence:   uence SEQ ID NO:  MAYKKTFXDIGDSYGELHAQARRREAVRRLLRLVRHRVLLHLLRAVLHAR   160 GSGSGLGHHHHHHRL  MASSFRLHNXGPSRXRHWDRLLTIYS IGVSTLANSLRVLHGVAHRGRHLG   161 GSGSGLGHHHHHHRL  MAYYNHPKLRQYLVKXLTRLRRYSYRELHDGDDHARQAHRGRLLQDLVDR GSGSGLGHHHHHHRL 162  MAYDPLHKASHSNHPQPYRYIGVIRHPLXRQS ISQI FKILLIRYLRKHRR 163 GSGSGLGHHHHHHRL   wherein X is the modified amino acid residue to which the oligosaccharide is linked. 33. The glycopeptide according to claim 31, wherein the glycopeptide comprises the sequence:   Sequence _ SEQ ID NO:   MAYKKTFXDIGDSYGELHAQARRREAVRRLLRLVRHRVLLHLLRAVLHAR 164  MASSFRLHNXGPSRXRHWDRLLTIYSIGVSTLANSLRVLHGVAHRGRHLG 165  MAYYNHPKLRQYLVKXLTRLRRYSYRELHDGDDHARQAHRGRLLQDLVDR 166  MAYDPLHKASHSNHPQPYRYIGVIRHPLXRQSISQIFKILLIRYLRKHRR 167 wherein X is the modified amino acid residue to which the oligosaccharide is linked. 34. The glycopeptide according to claim 23, wherein the glycopeptide comprises the sequence:   Sequence SEQ ID NO:   linker· 150  MANHSHGHNIGDIRDATCXLSN_CYHYNNRRKNRFTLFTLLRILVQKSLFR   GSGSGLGHHHHHHRL   |-linker-| 155  MANHSHGHNIGDIRDATCXLSN CYHYNNRRKNRFTLFTLLRILVQKSLFR   wherein X is the modified amino acid residue to which the oligosaccharide is linked, and the Cys-Cys linker is a bis-alkylbenzene group or bis-alkylpyridine group. 35. The glycopeptide according to claim 23, wherein the cyclic glycopeptide comprises a linker molecule between two cysteine sidechains. 36. The glycopeptide according to claim 35, wherein the linker molecule comprises     (i) -C(0)0-(CH2)n-CH3, where n is 0 to 6 or (ii) an immunogenic carrier molecule. 37. An immunogenic conjugate comprising a glycopeptide according to one of claims 1 to 26 covalently or non-covalently bound to an immunogenic carrier molecule. 38. The immunogenic conjugate according to claim 37, wherein the immunogenic carrier molecule is selected from the group consisting of bovine serum albumin, chicken egg ovalbumin, keyhole limpet hemocyanin, tetanus toxoid, diphtheria toxoid, thyroglobulin, a pneumococcal capsular polysaccharide, CRM 197, and a meningococcal outer membrane protein. 39. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a glycopeptide according to one of claims 1 to 36 or an immunogenic conjugate according to claim 37 or 38. 40. The pharmaceutical composition according to claim 39, wherein the glycopeptide is present. 41. The pharmaceutical composition according to claim 39, wherein the immunogenic conjugate is present. 42. The pharmaceutical composition according to claim 39, further comprising an adjuvant. 43. The pharmaceutical composition according to claim 42, wherein the adjuvant comprises aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, beryllium sulfate, silica, kaolin, carbon, water-in-oil emulsions, oil-in-water emulsions, muramyl dipeptide, bacterial endotoxin, lipid, Quil A, non-infective Bor detella pertussis, QS-21, monophosphoryl lipid A, an alpha-galactosylceramide derivative, or PamCys-type lipids. 44. The pharmaceutical composition according to one of claims 39 to 43 wherein the pharmaceutically acceptable carrier is a buffered saline solution. 45. The pharmaceutical composition according to one of claims 39 to 43, further comprising one or more additives or preservatives, or both. 46. The pharmaceutical composition according to one of claims 39 to 43, wherein the composition is present as a single dosage unit comprising about 1 pg to about 5 mg of the glycopeptide. 47. A method of inducing an immune response in an individual comprising:   administering to an individual a glycopeptide according to one of claims 1 to 36, an immunogenic conjugate according to claim 37 or 38, or a pharmaceutical composition according to one of claims 39 to 46, wherein said administering is effective to induce an immune response against the glycopeptide. 48. A method of inhibiting viral infection comprising:   administering to an individual an glycopeptide according to one of claims 1 to 36, an immunogenic conjugate according to claim 37 or 38, or a pharmaceutical composition according to one of claims 29 to 36, wherein said administering is effective to induce a neutralizing immune response against a virus pathogen. 49. A method for detecting a neutralizing antibody in serum comprising:   providing a glycopeptide according to any one of claims 1 to 36;   contacting the glycopeptide with serum from an individual; and   detecting whether the glycopeptide binds specifically to an antibody present in the serum, wherein said detecting is carried out using a label. 50. A method of preparing glycopeptides comprising:   providing an mRNA-displayed polypeptide having an N-terminal homopropargylglycine or allylglycine residue;   treating the mRNA-displayed polypeptide with an enzyme suitable to remove the N- terminal homopropargylglycine or allylglycine residue from the polypeptide; and   reacting the mRNA-displayed polypeptide recovered from said treating step with an oligosaccharide linked to a reactive moiety that is capable of reacting with a sidechain of one or more modified amino acids present in the polypeptide to thereby form a glycopeptide comprising one or more oligosaccharides linked to amino acid sidechains. 51. The method according to claim 50, wherein the N-terminal homopropargylglycine or allylglycine residue is formylated, and the enzyme is a first treatment with peptide   deformylase and a second treatment with methionine aminopeptidase. 52. The method according to claim 50, wherein the peptide includes an enterokinase cleavage sequence located within 1-10 residues of the N-terminus, and the enzyme is an enterokinase suitable to cleave the cleavage sequence.
法律状态
PENDING
专利类型码
A3A2
国别省市代码
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