[发明专利]一种新型非洲爪蟾胰高血糖素样肽-1(GLP-1)缀合肽及其应用

摘要

本发明涉及一种一种新型非洲爪蟾胰高血糖素样肽‑1（GLP‑1）缀合肽及其合成方法和应用。通过在非洲爪蟾GLP‑1的C端引入促螺旋序列，同时进行PEG化修饰，得到降糖活性保持和具有更长药理作用时间的非洲爪蟾GLP‑1类似物。本发明的非洲爪蟾GLP‑1类似物合成收率高、成本低，类似物的半衰期显著延长，生物活性得以显著提高。

主权项

1.一种非洲爪蟾胰高血糖素样肽-1(GLP-1)类似物，其特征在于，其结构为下式之一所示：/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Asn-Asp-Val-Cys(S-PEG anolog)-Glu-Tyr-Leu-Glu-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Leu-Ile-Lys-G1y-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Asn-Asp-Val-Thr-Cys(S-PEG anolog)-Tyr-Leu-Glu-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Asn-Asp-Val-Thr-Glu-Cys(S-PEG anolog)-Leu-Glu-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Asn-Asp-Val-Thr-Glu-Tyr-Cys(S-PEG anolog)-Glu-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Asn-Asp-Val-Thr-Glu-Tyr-Leu-Glu-Glu-Cys(S-PEGanolog)-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Asn-Asp-Val-Thr-Glu-Tyr-Leu-Glu-Glu-Lys-Cys(S-PEG anolog)-Ala-Lys-Glu-Phe-Tle-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-G1y-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Ash-Asp-Val-Thr-Glu-Tyr-Leu-Glu-Glu-Lys-Ala-Cys(S-PEGanolog)-Lys-G1u-Phe-Ile-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Ash-Asp-Val-Thr-Glu-Tyr-Leu-G1u-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Cys(S-PEG anolog)-Glu-Trp-Leu-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Ash-Asp-Val-Thr-Glu-Tyr-Leu-Glu-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Cys(S-PEG anolog)-Ile-Lys-Gly-Lys-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/nHis-Gly-Glu-Gly-Thr-Tyr-Thr-Ash-Asp-Val-Thr-Glu-Tyr-Leu-Glu-Glu-Lys-Ala-Ala-Lys-Glu-Phe-Ile-Glu-Trp-Leu-Ile-Lys-Gly-Cys(S-PEG anolog)-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂；/n其中Cys(S-PEG analog)选自/n /n这里：n选自30～80。/n