ME03709B - Fuzijski proteini - Google Patents
Fuzijski proteiniInfo
- Publication number
- ME03709B ME03709B MEP-2020-51A MEP202051A ME03709B ME 03709 B ME03709 B ME 03709B ME P202051 A MEP202051 A ME P202051A ME 03709 B ME03709 B ME 03709B
- Authority
- ME
- Montenegro
- Prior art keywords
- gly
- val
- ser
- glu
- pro
- Prior art date
Links
- 108020001507 fusion proteins Proteins 0.000 title claims description 21
- 102000037865 fusion proteins Human genes 0.000 title claims description 21
- 150000001413 amino acids Chemical group 0.000 claims description 20
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical group N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims 9
- 102000004877 Insulin Human genes 0.000 claims 8
- 108090001061 Insulin Proteins 0.000 claims 8
- 229940125396 insulin Drugs 0.000 claims 5
- 239000000710 homodimer Substances 0.000 claims 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 229940079288 Insulin receptor agonist Drugs 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- 108010005794 dulaglutide Proteins 0.000 claims 3
- 229960005175 dulaglutide Drugs 0.000 claims 3
- 230000004048 modification Effects 0.000 claims 3
- 238000012986 modification Methods 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims 1
- 101500025353 Homo sapiens Insulin A chain Proteins 0.000 claims 1
- 101500025354 Homo sapiens Insulin B chain Proteins 0.000 claims 1
- 229930195725 Mannitol Natural products 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims 1
- 239000000594 mannitol Substances 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 102000040430 polynucleotide Human genes 0.000 claims 1
- 108091033319 polynucleotide Proteins 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims 1
- 229920000053 polysorbate 80 Polymers 0.000 claims 1
- 229940068968 polysorbate 80 Drugs 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 28
- 108010078144 glutaminyl-glycine Proteins 0.000 description 27
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 27
- QMOQBVOBWVNSNO-UHFFFAOYSA-N 2-[[2-[[2-[(2-azaniumylacetyl)amino]acetyl]amino]acetyl]amino]acetate Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(O)=O QMOQBVOBWVNSNO-UHFFFAOYSA-N 0.000 description 25
- 108010016616 cysteinylglycine Proteins 0.000 description 19
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 18
- 241000880493 Leptailurus serval Species 0.000 description 17
- 108010048818 seryl-histidine Proteins 0.000 description 17
- XTHUKRLJRUVVBF-WHFBIAKZSA-N Cys-Gly-Ser Chemical compound SC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O XTHUKRLJRUVVBF-WHFBIAKZSA-N 0.000 description 15
- IWUFOVSLWADEJC-AVGNSLFASA-N Gln-His-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O IWUFOVSLWADEJC-AVGNSLFASA-N 0.000 description 15
- TWROVBNEHJSXDG-IHRRRGAJSA-N His-Leu-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O TWROVBNEHJSXDG-IHRRRGAJSA-N 0.000 description 15
- MXHCPCSDRGLRER-UHFFFAOYSA-N pentaglycine Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)NCC(O)=O MXHCPCSDRGLRER-UHFFFAOYSA-N 0.000 description 15
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 14
- IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 13
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 13
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 12
- AIQWYVFNBNNOLU-RHYQMDGZSA-N Leu-Thr-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O AIQWYVFNBNNOLU-RHYQMDGZSA-N 0.000 description 12
- TUIOUEWKFFVNLH-DCAQKATOSA-N Leu-Val-Cys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(O)=O TUIOUEWKFFVNLH-DCAQKATOSA-N 0.000 description 12
- 108010065920 Insulin Lispro Proteins 0.000 description 11
- JDMKQHSHKJHAHR-UHFFFAOYSA-N Phe-Phe-Leu-Tyr Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)CC1=CC=CC=C1 JDMKQHSHKJHAHR-UHFFFAOYSA-N 0.000 description 11
- 108010064235 lysylglycine Proteins 0.000 description 11
- CKOFNWCLWRYUHK-XHNCKOQMSA-N Glu-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CKOFNWCLWRYUHK-XHNCKOQMSA-N 0.000 description 10
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 description 10
- ZLNYBMWGPOKSLW-LSJOCFKGSA-N Val-Val-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLNYBMWGPOKSLW-LSJOCFKGSA-N 0.000 description 10
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 10
- 108010051110 tyrosyl-lysine Proteins 0.000 description 10
- YNQMEIJEWSHOEO-SRVKXCTJSA-N Asn-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O YNQMEIJEWSHOEO-SRVKXCTJSA-N 0.000 description 9
- QKCZZAZNMMVICF-DCAQKATOSA-N Gln-Leu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O QKCZZAZNMMVICF-DCAQKATOSA-N 0.000 description 9
- DHNXGWVNLFPOMQ-KBPBESRZSA-N Gly-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)CN DHNXGWVNLFPOMQ-KBPBESRZSA-N 0.000 description 9
- JHNJNTMTZHEDLJ-NAKRPEOUSA-N Ile-Ser-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O JHNJNTMTZHEDLJ-NAKRPEOUSA-N 0.000 description 9
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 9
- GOUWCZRDTWTODO-YDHLFZDLSA-N Phe-Val-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O GOUWCZRDTWTODO-YDHLFZDLSA-N 0.000 description 9
- UAYHMOIGIQZLFR-NHCYSSNCSA-N Pro-Gln-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O UAYHMOIGIQZLFR-NHCYSSNCSA-N 0.000 description 9
- ZLXKLMHAMDENIO-DCAQKATOSA-N Pro-Lys-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLXKLMHAMDENIO-DCAQKATOSA-N 0.000 description 9
- PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 description 9
- FIFDDJFLNVAVMS-RHYQMDGZSA-N Thr-Leu-Met Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O FIFDDJFLNVAVMS-RHYQMDGZSA-N 0.000 description 9
- PWKMJDQXKCENMF-MEYUZBJRSA-N Tyr-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O PWKMJDQXKCENMF-MEYUZBJRSA-N 0.000 description 9
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 9
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 9
- DPNWSMBUYCLEDG-CIUDSAMLSA-N Asp-Lys-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O DPNWSMBUYCLEDG-CIUDSAMLSA-N 0.000 description 8
- FITIQFSXXBKFFM-NRPADANISA-N Gln-Val-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FITIQFSXXBKFFM-NRPADANISA-N 0.000 description 8
- KASDBWKLWJKTLJ-GUBZILKMSA-N Glu-Glu-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O KASDBWKLWJKTLJ-GUBZILKMSA-N 0.000 description 8
- GRIRDMVMJJDZKV-RCOVLWMOSA-N Gly-Asn-Val Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O GRIRDMVMJJDZKV-RCOVLWMOSA-N 0.000 description 8
- HIAHVKLTHNOENC-HGNGGELXSA-N His-Glu-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HIAHVKLTHNOENC-HGNGGELXSA-N 0.000 description 8
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 8
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 8
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 8
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 8
- RCOUFINCYASMDN-GUBZILKMSA-N Ser-Val-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O RCOUFINCYASMDN-GUBZILKMSA-N 0.000 description 8
- BDGBHYCAZJPLHX-HJGDQZAQSA-N Thr-Lys-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BDGBHYCAZJPLHX-HJGDQZAQSA-N 0.000 description 8
- HIINQLBHPIQYHN-JTQLQIEISA-N Tyr-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HIINQLBHPIQYHN-JTQLQIEISA-N 0.000 description 8
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 8
- 108010057821 leucylproline Proteins 0.000 description 8
- 108010070643 prolylglutamic acid Proteins 0.000 description 8
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 8
- 108010080629 tryptophan-leucine Proteins 0.000 description 8
- 108010017949 tyrosyl-glycyl-glycine Proteins 0.000 description 8
- 108010027345 wheylin-1 peptide Proteins 0.000 description 8
- LGCVSPFCFXWUEY-IHPCNDPISA-N Asn-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N LGCVSPFCFXWUEY-IHPCNDPISA-N 0.000 description 7
- KOHBWQDSVCARMI-BWBBJGPYSA-N Cys-Cys-Thr Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KOHBWQDSVCARMI-BWBBJGPYSA-N 0.000 description 7
- DHNWZLGBTPUTQQ-QEJZJMRPSA-N Gln-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N DHNWZLGBTPUTQQ-QEJZJMRPSA-N 0.000 description 7
- GLWXKFRTOHKGIT-ACZMJKKPSA-N Glu-Asn-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GLWXKFRTOHKGIT-ACZMJKKPSA-N 0.000 description 7
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 7
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 7
- BPCLDCNZBUYGOD-BPUTZDHNSA-N Glu-Trp-Glu Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 BPCLDCNZBUYGOD-BPUTZDHNSA-N 0.000 description 7
- YQPFCZVKMUVZIN-AUTRQRHGSA-N Glu-Val-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQPFCZVKMUVZIN-AUTRQRHGSA-N 0.000 description 7
- XMPXVJIDADUOQB-RCOVLWMOSA-N Gly-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)CNC(=O)C[NH3+] XMPXVJIDADUOQB-RCOVLWMOSA-N 0.000 description 7
- UUYBFNKHOCJCHT-VHSXEESVSA-N Gly-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN UUYBFNKHOCJCHT-VHSXEESVSA-N 0.000 description 7
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- ODTZHNZPINULEU-KKUMJFAQSA-N Lys-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N ODTZHNZPINULEU-KKUMJFAQSA-N 0.000 description 1
- JHNOXVASMSXSNB-WEDXCCLWSA-N Lys-Thr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JHNOXVASMSXSNB-WEDXCCLWSA-N 0.000 description 1
- KNYPNEYICHHLQL-ACRUOGEOSA-N Phe-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 KNYPNEYICHHLQL-ACRUOGEOSA-N 0.000 description 1
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 1
- ULWBBFKQBDNGOY-RWMBFGLXSA-N Pro-Lys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)O ULWBBFKQBDNGOY-RWMBFGLXSA-N 0.000 description 1
- AFWBWPCXSWUCLB-WDSKDSINSA-N Pro-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H]1CCC[NH2+]1 AFWBWPCXSWUCLB-WDSKDSINSA-N 0.000 description 1
- MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 1
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 1
- HMRAQFJFTOLDKW-GUBZILKMSA-N Ser-His-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O HMRAQFJFTOLDKW-GUBZILKMSA-N 0.000 description 1
- XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 1
- LRZLZIUXQBIWTB-KATARQTJSA-N Ser-Lys-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LRZLZIUXQBIWTB-KATARQTJSA-N 0.000 description 1
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 1
- WRQLCVIALDUQEQ-UNQGMJICSA-N Thr-Phe-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WRQLCVIALDUQEQ-UNQGMJICSA-N 0.000 description 1
- IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 1
- BKVICMPZWRNWOC-RHYQMDGZSA-N Thr-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O BKVICMPZWRNWOC-RHYQMDGZSA-N 0.000 description 1
- DQDXHYIEITXNJY-BPUTZDHNSA-N Trp-Gln-Gln Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N DQDXHYIEITXNJY-BPUTZDHNSA-N 0.000 description 1
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 1
- KSCVLGXNQXKUAR-JYJNAYRXSA-N Tyr-Leu-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KSCVLGXNQXKUAR-JYJNAYRXSA-N 0.000 description 1
- AOIZTZRWMSPPAY-KAOXEZKKSA-N Tyr-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)O AOIZTZRWMSPPAY-KAOXEZKKSA-N 0.000 description 1
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 1
- DIOSYUIWOQCXNR-ONGXEEELSA-N Val-Lys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O DIOSYUIWOQCXNR-ONGXEEELSA-N 0.000 description 1
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 1
- 108010091078 rigin Proteins 0.000 description 1
- 108010020532 tyrosyl-proline Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
Description
SPISAK SLJEDOVA
<110> Eli Lilly and Company
<120> FUZIJSKI PROTEINI
<130> X20356
<150> 62/158079
<151> 2015-05-07
<160> 25
<170> PatentIn verzija 3.5
<210> 1
<211> 30
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (1)..(1)
<223> Xaa na položaju 1 je Phe, Gln ili Ala
<220>
<221> Miješana svojstva
<222> (2)..(2)
<223> Xaa na položaju 2 je Val ili Gly
<220>
<221> Miješana svojstva
<222> (3)..(3)
<223> Xaa na položaju 3 je Asn, Lys, Asp, Gly, Gln, Ala ili Glu
<220>
<221> Miješana svojstva
<222> (16)..(16)
<223> Xaa na položaju 16 je Glu, Tyr, Gln ili His
<220>
<221> Miješana svojstva
<222> (25)..(25)
<223> Xaa na položaju 25 je His ili Phe
<220>
<221> Miješana svojstva
<222> (27)..(27)
<223> Xaa na položaju 27 je Gly, Thr, Ser, His, Val, ili je odsutna
<220>
<221> Miješana svojstva
<222> (28)..(28)
<223> Xaa na položaju 28 je Gly, Glu, Pro, Lys, Asp, Ser, His, ili je odsutna
<220>
<221> Miješana svojstva
<222> (29)..(29)
<223> Xaa na položaju 29 je Gly, Glu, Lys, Pro, Gln, Asp, His, ili je odsutna
<220>
<221> Miješana svojstva
<222> (30)..(30)
<223> Xaa na položaju 30 je Gly, Thr, Ser, Glu, Lys, Ala, ili je odsutna
<400> 1
Xaa Xaa Xaa Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Xaa
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe Xaa Tyr Xaa Xaa Xaa Xaa
20 25 30
<210> 2
<211> 22
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (10)..(10)
<223> Xaa na položaju 10 je Thr ili Ile
<220>
<221> Miješana svojstva
<222> (14)..(14)
<223> Xaa na položaju 14 je Asp, Tyr, Gln ili Glu
<220>
<221> Miješana svojstva
<222> (21)..(21)
<223> Xaa na položaju 21 je Gly, Asn, Ser, ili Ala
<220>
<221> Miješana svojstva
<222> (22)..(22)
<223> Xaa na položaju 22 je bilo koja prirodna aminokiselina, ili je odsutna
<400> 2
Gly Ile Val Glu Gln Cys Cys Thr Ser Xaa Cys Ser Leu Xaa Gln Leu
1 5 10 15
Glu Asn Tyr Cys Xaa Xaa
20
<210> 3
<211> 7
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (1)..(1)
<223> Xaa na položaju 1 je Gly ili je odsutna
<220>
<221> Miješana svojstva
<222> (3)..(3)
<223> Xaa na položaju 3 je Gly, Ser, ili je odsutna
<400> 3
Xaa Gly Xaa Gly Gly Gly Gly
1 5
<210> 4
<211> 59
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (1)..(1)
<223> Xaa na položaju 1 je Phe, Gln, ili Ala
<220>
<221> Miješana svojstva
<222> (2)..(2)
<223> Xaa na položaju 2 je Val ili Gly
<220>
<221> Miješana svojstva
<222> (3)..(3)
<223> Xaa na položaju 3 je Asn, Lys, Asp, Gly, Gln, Ala, ili Glu
<220>
<221> Miješana svojstva
<222> (16)..(16)
<223> Xaa na položaju 16 je Glu, Tyr, Gln, ili His
<220>
<221> Miješana svojstva
<222> (25)..(25)
<223> Xaa na položaju 25 je His ili Phe
<220>
<221> Miješana svojstva
<222> (27)..(27)
<223> Xaa na položaju 27 je Gly, Thr, Ser, His, Val, ili je odsutna
<220>
<221> Miješana svojstva
<222> (28)..(28)
<223> Xaa na položaju 28 je Gly, Glu, Pro, Lys, Asp, Ser, His, ili je odsutna
<220>
<221> Miješana svojstva
<222> (29)..(29)
<223> Xaa na položaju 29 je Gly, Glu, Lys, Pro, Gln, Asp, His, ili je odsutna
<220>
<221> Miješana svojstva
<222> (30)..(30)
<223> Xaa na položaju 30 je Gly, Thr, Ser, Glu, Lys, Ala, ili je odsutna
<220>
<221> Miješana svojstva
<222> (31)..(31)
<223> Xaa na položaju 31 je Gly ili je odsutna
<220>
<221> Miješana svojstva
<222> (33)..(33)
<223> Xaa na položaju 33 je Gly, Ser, ili je odsutna
<220>
<221> Miješana svojstva
<222> (47)..(47)
<223> Xaa na položaju 47 je Thr ili Ile
<220>
<221> Miješana svojstva
<222> (51)..(51)
<223> Xaa na položaju 51 je Asp, Tyr, Gln, ili Glu
<220>
<221> Miješana svojstva
<222> (58)..(58)
<223> Xaa na položaju 58 je Gly, Asn, Ser, ili Ala
<220>
<221> Miješana svojstva
<222> (59)..(59)
<223> Xaa na položaju 59 je bilo koja prirodna aminokiselina, ili je odsutna
<400> 4
Xaa Xaa Xaa Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Xaa
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe Xaa Tyr Xaa Xaa Xaa Xaa Xaa Gly
20 25 30
Xaa Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Xaa Cys
35 40 45
Ser Leu Xaa Gln Leu Glu Asn Tyr Cys Xaa Xaa
50 55
<210> 5
<211> 58
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 5
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys
35 40 45
Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly
50 55
<210> 6
<211> 22
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (5)..(5)
<223> Xaa na položaju 5 je Gln ili Glu
<220>
<221> Miješana svojstva
<222> (10)..(10)
<223> Xaa na položaju 10 je Gln ili Glu
<220>
<221> Miješana svojstva
<222> (15)..(15)
<223> Xaa na položaju 15 je Gln ili Glu
<220>
<221> Miješana svojstva
<222> (20)..(20)
<223> Xaa na položaju 20 je Gly, Glu, Gln, ili je odsutna
<220>
<221> Miješana svojstva
<222> (21)..(21)
<223> Xaa na položaju 21 je Gly ili odsutna
<220>
<221> Miješana svojstva
<222> (22)..(22)
<223> Xaa na položaju 21 je Gly ili je odsutna
<220>
<221> Miješana svojstva
<222> (22)..(22)
<223> Xaa na položaju 22 je Gly ili je odsutna
<400> 6
Gly Gly Gly Gly Xaa Gly Gly Gly Gly Xaa Gly Gly Gly Gly Xaa Gly
1 5 10 15
Gly Gly Gly Xaa Xaa Xaa
20
<210> 7
<211> 20
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 7
Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly
1 5 10 15
Gly Gly Gly Gly
20
<210> 8
<211> 222
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (16)..(16)
<223> Xaa na položaju 16 je Phe, Gln ili Glu
<220>
<221> Miješana svojstva
<222> (18)..(18)
<223> Xaa na položaju 18 je Phe, Gln ili Glu
<220>
<221> Miješana svojstva
<222> (37)..(37)
<223> Xaa na položaju 37 je Val ili Thr
<220>
<221> Miješana svojstva
<222> (39)..(39)
<223> Xaa na položaju 39 je Val ili Thr
<220>
<221> Miješana svojstva
<222> (72)..(72)
<223> Xaa na položaju 72 je Asn, Asp ili Gln
<220>
<221> Miješana svojstva
<222> (222)..(222)
<223> Xaa na položaju 222 je Lys ili je odsutna
<400> 8
Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Xaa
1 5 10 15
Leu Xaa Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
20 25 30
Glu Val Thr Cys Xaa Val Xaa Asp Val Ser His Glu Asp Pro Glu Val
35 40 45
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
50 55 60
Lys Pro Arg Glu Glu Gln Tyr Xaa Ser Thr Tyr Arg Val Val Ser Val
65 70 75 80
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
85 90 95
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
100 105 110
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
115 120 125
Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
130 135 140
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
145 150 155 160
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
165 170 175
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
180 185 190
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
195 200 205
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Xaa
210 215 220
<210> 9
<211> 223
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (17)..(17)
<223> Xaa na položaju 17 je Phe, Gln ili Glu
<220>
<221> Miješana svojstva
<222> (19)..(19)
<223> Xaa na položaju 19 je Phe, Gln ili Glu
<220>
<221> Miješana svojstva
<222> (38)..(38)
<223> Xaa na položaju 38 je Val ili Thr
<220>
<221> Miješana svojstva
<222> (40)..(40)
<223> Xaa na položaju 40 je Val ili Thr
<220>
<221> Miješana svojstva
<222> (73)..(73)
<223> Xaa na položaju 73 je Asn, Asp ili Gln
<220>
<221> Miješana svojstva
<222> (185)..(185)
<223> Xaa na položaju 185 je Arg ili Lys
<220>
<221> Miješana svojstva
<222> (223)..(223)
<223> Xaa na položaju 223 je Lys ili je odsutna
<400> 9
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
1 5 10 15
Xaa Leu Xaa Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
20 25 30
Pro Glu Val Thr Cys Xaa Val Xaa Asp Val Ser Gln Glu Asp Pro Glu
35 40 45
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
50 55 60
Thr Lys Pro Arg Glu Glu Gln Phe Xaa Ser Thr Tyr Arg Val Val Ser
65 70 75 80
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
85 90 95
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
100 105 110
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
115 120 125
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
130 135 140
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
145 150 155 160
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
165 170 175
Asp Gly Ser Phe Phe Leu Tyr Ser Xaa Leu Thr Val Asp Lys Ser Arg
180 185 190
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
195 200 205
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Xaa
210 215 220
<210> 10
<211> 222
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (16)..(16)
<223> Xaa na položaju 16 je Phe, Gln, ili Glu
<220>
<221> Miješana svojstva
<222> (18)..(18)
<223> Xaa na položaju 18 je Phe, Gln, ili Glu
<220>
<221> Miješana svojstva
<222> (37)..(37)
<223> Xaa na položaju 37 je Val ili Thr
<220>
<221> Miješana svojstva
<222> (39)..(39)
<223> Xaa na položaju 39 je Val ili Thr
<220>
<221> Miješana svojstva
<222> (72)..(72)
<223> Xaa na položaju 72 je Asn, Asp, ili Gln
<220>
<221> Miješana svojstva
<222> (222)..(222)
<223> Xaa na položaju 222 je Lys ili je odsutna
<400> 10
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Xaa
1 5 10 15
Leu Xaa Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
20 25 30
Glu Val Thr Cys Xaa Val Xaa Asp Val Ser His Glu Asp Pro Glu Val
35 40 45
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
50 55 60
Lys Pro Arg Glu Glu Gln Phe Xaa Ser Thr Phe Arg Val Val Ser Val
65 70 75 80
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
85 90 95
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
100 105 110
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
115 120 125
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
130 135 140
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
145 150 155 160
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp
165 170 175
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
180 185 190
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
195 200 205
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Xaa
210 215 220
<210> 11
<211> 303
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<220>
<221> Miješana svojstva
<222> (1)..(1)
<223> Xaa na položaju 1 je Phe, Gln, ili Ala
<220>
<221> Miješana svojstva
<222> (2)..(2)
<223> Xaa na položaju 2 je Val ili Gly
<220>
<221> Miješana svojstva
<222> (3)..(3)
<223> Xaa na položaju 3 je Asn, Lys, Asp, Gly, Gln, Ala, ili Glu
<220>
<221> Miješana svojstva
<222> (16)..(16)
<223> Xaa na položaju 16 je Glu, Tyr, Gln, ili His
<220>
<221> Miješana svojstva
<222> (25)..(25)
<223> Xaa na položaju 25 je His ili Phe
<220>
<221> Miješana svojstva
<222> (27)..(27)
<223> Xaa na položaju 27 je Gly, Thr, Ser, His, Val, ili je odsutna
<220>
<221> Miješana svojstva
<222> (28)..(28)
<223> Xaa na položaju 28 je Gly, Glu, Pro, Lys, Asp, Ser, His, ili je odsutna
<220>
<221> Miješana svojstva
<222> (29)..(29)
<223> Xaa na položaju 29 je Gly, Glu, Lys, Pro, Gln, Asp, His, ili je odsutna
<220>
<221> Miješana svojstva
<222> (30)..(30)
<223> Xaa na položaju 30 je Gly, Thr, Ser, Glu, Lys, Ala, ili je odsutna
<220>
<221> Miješana svojstva
<222> (31)..(31)
<223> Xaa na položaju 31 je Gly, ili je odsutna
<220>
<221> Miješana svojstva
<222> (33)..(33)
<223> Xaa na položaju 33 je Gly, Ser, ili je odsutna
<220>
<221> Miješana svojstva
<222> (47)..(47)
<223> Xaa na položaju 47 je Thr ili Ile
<220>
<221> Miješana svojstva
<222> (51)..(51)
<223> Xaa na položaju 51 je Asp, Tyr, Gln, ili Glu
<220>
<221> Miješana svojstva
<222> (58)..(58)
<223> Xaa na položaju 58 je Gly, Asn, Ser ili Ala
<220>
<221> Miješana svojstva
<222> (59)..(59)
<223> Xaa na položaju 59 je bilo koja prirodna aminokiselina, ili je odsutna
<220>
<221> Miješana svojstva
<222> (64)..(64)
<223> Xaa na položaju 64 je Gln ili Glu
<220>
<221> Miješana svojstva
<222> (69)..(69)
<223> Xaa na položaju 69 je Gln ili Glu
<220>
<221> Miješana svojstva
<222> (74)..(74)
<223> Xaa na položaju 74 je Gln ili Glu
<220>
<221> Miješana svojstva
<222> (79)..(79)
<223> Xaa na položaju 79 je Gly, Glu, Gln, ili je odsutna
<220>
<221> Miješana svojstva
<222> (80)..(80)
<223> Xaa na položaju 80 je Gly ili je odsutna
<220>
<221> Miješana svojstva
<222> (81)..(81)
<223> Xaa na položaju 81 je Gly ili je odsutna
<220>
<221> Miješana svojstva
<222> (82)..(82)
<223> Xaa na položaju 82 je Glu ili Pro
<220>
<221> Miješana svojstva
<222> (90)..(90)
<223> Xaa na položaju 90 je Glu ili Pro
<220>
<221> Miješana svojstva
<222> (91)..(91)
<223> Xaa na položaju 91 je Ala and Val
<220>
<221> Miješana svojstva
<222> (94)..(94)
<223> Xaa na položaju 94 je Gly ili je odsutna
<220>
<221> Miješana svojstva
<222> (125)..(125)
<223> Xaa na položaju 125 je Gln ili His
<220>
<221> Miješana svojstva
<222> (157)..(157)
<223> Xaa na položaju 157 je Tyr ili Phe
<220>
<221> Miješana svojstva
<222> (166)..(166)
<223> Xaa na položaju 166 je Leu ili Val
<220>
<221> Miješana svojstva
<222> (187)..(187)
<223> Xaa na položaju 187 je Ser ili Ala
<220>
<221> Miješana svojstva
<222> (188)..(188)
<223> Xaa na položaju 188 je Ser ili Pro
<220>
<221> Miješana svojstva
<222> (196)..(196)
<223> Xaa na položaju 196 je Ala ili Thr
<220>
<221> Miješana svojstva
<222> (212)..(212)
<223> Xaa na položaju 212 je Gln ili Arg
<220>
<221> Miješana svojstva
<222> (254)..(254)
<223> Xaa na položaju 254 je Val ili Met
<220>
<221> Miješana svojstva
<222> (266)..(266)
<223> Xaa na položaju 266 je Arg ili Lys
<220>
<221> Miješana svojstva
<222> (276)..(276)
<223> Xaa na položaju 276 je Glu ili Gln
<220>
<221> Miješana svojstva
<222> (302)..(302)
<223> Xaa na položaju 302 je Leu ili Pro
<400> 11
Xaa Xaa Xaa Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Xaa
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe Xaa Tyr Xaa Xaa Xaa Xaa Xaa Gly
20 25 30
Xaa Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Xaa Cys
35 40 45
Ser Leu Xaa Gln Leu Glu Asn Tyr Cys Xaa Xaa Gly Gly Gly Gly Xaa
50 55 60
Gly Gly Gly Gly Xaa Gly Gly Gly Gly Xaa Gly Gly Gly Gly Xaa Xaa
65 70 75 80
Xaa Xaa Cys Pro Pro Cys Pro Ala Pro Xaa Xaa Ala Gly Xaa Pro Ser
85 90 95
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
100 105 110
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Xaa Glu Asp Pro
115 120 125
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
130 135 140
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Xaa Arg Val Val
145 150 155 160
Ser Val Leu Thr Val Xaa His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
165 170 175
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Xaa Xaa Ile Glu Lys Thr
180 185 190
Ile Ser Lys Xaa Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
195 200 205
Pro Pro Ser Xaa Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
210 215 220
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
225 230 235 240
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Xaa Leu Asp
245 250 255
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Xaa Leu Thr Val Asp Lys Ser
260 265 270
Arg Trp Gln Xaa Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
275 280 285
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Xaa Gly
290 295 300
<210> 12
<211> 299
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 12
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys
35 40 45
Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly
50 55 60
Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Glu Cys
65 70 75 80
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
85 90 95
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
100 105 110
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe
115 120 125
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
130 135 140
Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr
145 150 155 160
Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
165 170 175
Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr
180 185 190
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
195 200 205
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
210 215 220
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
225 230 235 240
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser
245 250 255
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
260 265 270
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
275 280 285
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
290 295
<210> 13
<211> 21
<212> PRT
<213> Homo sapiens
<400> 13
Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu
1 5 10 15
Glu Asn Tyr Cys Asn
20
<210> 14
<211> 30
<212> PRT
<213> Homo sapiens
<400> 14
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr
20 25 30
<210> 15
<211> 7
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 15
Gly Gly Ser Gly Gly Gly Gly
1 5
<210> 16
<211> 300
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 16
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Glu Glu Thr Gly Gly
20 25 30
Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser
35 40 45
Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Ser Gly Gly
50 55 60
Gly Gly Ser Gly Gly Gly Gly Ser Glu Ser Lys Tyr Gly Pro Pro Cys
65 70 75 80
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu
85 90 95
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
100 105 110
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
115 120 125
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
130 135 140
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
145 150 155 160
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
165 170 175
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
180 185 190
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
195 200 205
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
210 215 220
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
225 230 235 240
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
245 250 255
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
260 265 270
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
275 280 285
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
290 295 300
<210> 17
<211> 302
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 17
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys
35 40 45
Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly
50 55 60
Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly
65 70 75 80
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
85 90 95
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
100 105 110
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
115 120 125
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
130 135 140
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
145 150 155 160
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
165 170 175
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
180 185 190
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
195 200 205
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
210 215 220
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
225 230 235 240
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
245 250 255
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
260 265 270
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
275 280 285
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
290 295 300
<210> 18
<211> 297
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 18
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Ser
20 25 30
Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser
35 40 45
Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Glu Gly Gly
50 55 60
Gly Gly Glu Gly Gly Gly Gly Glu Gly Gly Gly Gly Glu Cys Pro Pro
65 70 75 80
Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro
85 90 95
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
100 105 110
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp
115 120 125
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
130 135 140
Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val
145 150 155 160
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
165 170 175
Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
180 185 190
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu
195 200 205
Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
210 215 220
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
225 230 235 240
Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe
245 250 255
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
260 265 270
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
275 280 285
Gln Lys Ser Leu Ser Leu Ser Pro Gly
290 295
<210> 19
<211> 302
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 19
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys
35 40 45
Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly
50 55 60
Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly
65 70 75 80
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
85 90 95
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
100 105 110
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
115 120 125
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
130 135 140
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
145 150 155 160
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
165 170 175
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
180 185 190
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
195 200 205
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
210 215 220
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
225 230 235 240
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
245 250 255
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
260 265 270
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
275 280 285
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
290 295 300
<210> 20
<211> 302
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 20
Phe Val Gly Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly
20 25 30
Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys
35 40 45
Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly
50 55 60
Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly
65 70 75 80
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
85 90 95
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
100 105 110
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
115 120 125
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
130 135 140
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
145 150 155 160
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
165 170 175
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
180 185 190
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
195 200 205
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
210 215 220
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
225 230 235 240
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
245 250 255
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
260 265 270
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
275 280 285
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
290 295 300
<210> 21
<211> 297
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 21
Ala Gly Gly Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Ser
20 25 30
Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser
35 40 45
Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly Gly
50 55 60
Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Glu Cys Pro Pro
65 70 75 80
Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro
85 90 95
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
100 105 110
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp
115 120 125
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
130 135 140
Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val
145 150 155 160
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
165 170 175
Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly
180 185 190
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu
195 200 205
Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
210 215 220
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
225 230 235 240
Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe
245 250 255
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
260 265 270
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
275 280 285
Gln Lys Ser Leu Ser Leu Ser Pro Gly
290 295
<210> 22
<211> 299
<212> PRT
<213> Umjetni slijed
<220>
<223> Sintetski konstrukt
<400> 22
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe His Tyr Thr Pro Lys Thr Gly Gly
20 25 30
Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys
35 40 45
Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly
50 55 60
Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Glu Cys
65 70 75 80
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
85 90 95
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Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe
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Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn
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Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
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Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu
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Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
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Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly
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Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly
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Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Glu Cys
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Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
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Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe
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Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr
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Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
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Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr
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Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
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Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
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Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
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Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser
245 250 255
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
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Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
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<210> 25
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<212> PRT
<213> Homo sapiens
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Claims (23)
1. Fuzijski protein, naznačen time što sadrži: a) agonist inzulinskog receptora koji ima opću formulu Z1-Z2-Z3, gdje: i) Z1 je analog inzulinskog lanca B, koji ima aminokiselinski slijed: X1X2X3QHLCGSHLVEALX4LVCGERGFX5YX6X7X8X9 gdje je X1 F, Q ili A; X2 je V ili G; X3 je N, K, D, G, Q, A ili E; X4 je E, Y, Q, ili H; X5 je H ili F; X6 je G, T, S, H, V ili je odsutan; X7 je G, E, P, K, D, S, H ili je odsutan; X8 je G, E, K, P, Q, D, H ili je odsutan; X9 je G, T, S, E, K, A ili je odsutan, uz uvjet da analog inzulinskog lanca B sadrži najmanje jednu modifikaciju u odnosu na aminokiselinski slijed lanca B molekule ljudskog inzulina na X4, X5, X6, X7, X8 ili X9 (SEQ ID NO:1); ii) Z2 je prva peptidna spojnica, koja ima 5 do 10 aminokiselina, gdje su najmanje 5 navedenih aminokiselina ostaci G; i iii) Z3 je analog inzulinskog lanca A, koji ima aminokiselinski slijed: GIVEQCCTSX1CSLX2QLENYCX3X4 gdje je X1 T ili I; X2 je D, Y, Q ili E; X3 je G, N, S ili A; i X4 je bilo koja prirodna aminokiselina, ili je odsutan, uz uvjet da ako je X3 N, X4 mora biti aminokiselina koja nije G ili N (SEQ ID NO:2); b) druga peptidna spojnica ima između 10 i 25 aminokiselina, gdje su najmanje 50% navedenih aminokiselina ostaci G; i c) Fc područje ljudskog IgG; gdje je C-terminalni ostatak agonista inzulinskog receptora izravno fuzioniran s N-terminalnim ostatkom druge peptidne spojnice, a C-terminalni ostatak druge peptidne spojnice je izravno fuzioniran s N-terminalnim ostatkom Fc područja ljudskog IgG.
2. Fuzijski protein u skladu s patentnim zahtjevom 1, naznačen time: analog inzulinskog lanca B sadrži najmanje jednu modifikaciju u odnosu na aminokiselinski slijed ljudskog inzulinskog lanca B na X4 ili X5 u SEQ ID NO:1; i analog inzulinskog lanca A sadrži najmanje jednu modifikaciju u odnosu na aminokiselinski slijed ljudskog inzulinskog lanca A na X1 ili X2 u SEQ ID NO:2.
3. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačen time što: analog inzulinskog lanca B ima slijed SEQ ID NO:1, gdje: X1 je F; X2 je V; X3 je N ili D; X4 je E; X5 je H; i analog inzulinskog lanca A ima slijed SEQ ID NO:2, gdje: X1 je I ili T; X2 je D; X3 je G; i X4 je odsutan.
4. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-3, naznačen time što analog inzulinskog lanca B ima slijed SEQ ID NO:1, gdje je svaki od X6-X9 G.
5. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačen time što prva peptidna spojnica ima sljedeći aminokiselinski slijed: X1GX2GGGG gdje je X1 G ili je odsutan; i X2 je G, S ili je odsutan (SEQ ID NO:3).
6. Fuzijski protein u skladu s patentnim zahtjevom 5, naznačen time što su X1 i X2 u SEQ ID NO:3 G odnosno S.
7. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-6, naznačen time što agonist inzulinskog receptora ima sljedeći aminokiselinski slijed: FVNQHLCGSHLVEALELVCGERGFHYGGGGGGSGGGGGIVEQCCTSTCSLDQLENYCG (SEQ ID NO:5).
8. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-7, naznačen time što druga peptidna spojnica sadrži peptid koji ima slijed [GGGGX]n gdje je X Q, E ili S; i gdje je n 2-5.
9. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-8, naznačen time što druga peptidna spojnica ima sljedeći aminokiselinski slijed: GGGGX1GGGGX2GGGGX3GGGGX4X5X6 X1 je Q ili E X2 je Q ili E X3 je Q ili E X4 je G, E, Q ili je odsutan X5 je G ili odsutan; i X6 je G ili je odsutan (SEQ ID NO:6).
10. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-9, naznačen time što druga peptidna spojnica ima sljedeći aminokiselinski slijed: GGGGQGGGGQGGGGQGGGGG (SEQ ID NO:7).
11. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-10, naznačen time što je Fc područje ljudskog IgG Fc područje u IgG1, IgG2 ili IgG4.
12. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-11, naznačen time što Fc područje ljudskog IgG sadrži aminokiselinski slijed kojeg se bira iz skupine koju čine SEQ ID NO:8, SEQ ID NO:9 i SEQ ID NO:10.
13. Fuzijski protein, naznačen time što ima aminokiselinski slijed SEQ ID NO:12.
14. Homodimer, naznačen time što je homodimer dva fuzijska proteina u skladu s bilo kojim od patentnih zahtjeva 1-13.
15. Farmaceutski pripravak, naznačen time što sadrži bilo fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-13 ili homodimer u skladu s patentnim zahtjevom 14, te najmanje jednu pomoćnu tvar.
16. Farmaceutski pripravak u skladu s patentnim zahtjevom 15, naznačen time što dodatno sadrži citrat, limunsku kiselinu, polisorbat 80, te manitol.
17. Farmaceutski pripravak u skladu s patentnim zahtjevom 15 ili patentnim zahtjevom 16, naznačen time što se pH kreće od otprilike 6,0 do otprilike 6,75.
18. Farmaceutski pripravak u skladu s bilo kojim od patentnih zahtjeva 15 do 17, naznačen time što dodatno sadrži dulaglutid.
19. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-13, naznačen time što je namijenjen upotrebi u terapiji.
20. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-13, naznačen time što je namijenjen upotrebi u liječenju dijabetesa melitusa.
21. Fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-13, naznačen time što je namijenjen upotrebi u istodobnoj, odvojenoj ili uzastopnoj kombinaciji s dulaglutidom, kod liječenja dijabetesa melitusa.
22. Homodimer u skladu s patentnim zahtjevom 14, naznačen time što je namijenjen upotrebi u istodobnoj, odvojenoj ili uzastopnoj kombinaciji s dulaglutidom, kod liječenja dijabetesa melitusa.
23. Polinukleotid, naznačen time što kodira fuzijski protein u skladu s bilo kojim od patentnih zahtjeva 1-13.
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| EP16721605.0A EP3292141B1 (en) | 2015-05-07 | 2016-04-28 | Fusion proteins |
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