[发明专利]微波促进固相合成胰高血糖素样肽－1(GLP－1)类似物及其应用

权利要求书

1.一种含有式I(SEQ.ID NO：1)结构的胰高血糖素样肽-1(GLP-1)类似物，得到的胰高血糖素样肽-1(GLP-1)类似物；其特征在于其结构具有以下形式：

His-Xaa₁-Xaa₂-Gly-Thr-Phe-Thr-Ser-Asp-Xaa₃-Ser-Ser-Tyr-Leu-Glu-Xaa₄-Gln-Ala-Ala-Lys-Xaa₅-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Xaa₆(SEQ.IDNO：1)

Xaa₁：Asp，Asn，Arg，Lys，His，Glu，Gln，Trp，Phe，Tyr，Met，D-Gly，D-VaL，D-Leu，D-Ile，D-Ser，或D-Thr；

Xaa₂：Glu，或Pro；

Xaa₃：Val，或Leu；

Xaa₄：Gly，Glu，Gln，Trp，Phe，Tyr，Met，D-Gly，D-VaL，D-Leu，D-Ile，D-Ser，D-Glu，D-Gln，D-Trp，或D-Met；

Xaa₅：Glu，或Leu；

Xaa₆：Gly，或-NH₂。

2.根据权利要求1所述的多肽，具有如下序列：

His-D-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：2)；

His-Asn-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：3)；

His-Trp-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：4)；

His-Tyr-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：5)；

His-Met-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：6)；

His-Glu-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：7)；

His-D-Val-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：8)；

His-D-Leu-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：9)；

His-D-Ser-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：10)；

His-D-Ile-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：11)；

His-D-Thr-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：12)；

His-Ser-Pro-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：13)；

His-Val-Pro-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：14)；

His-Leu-Pro-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：15)；

His-Gly-Pro-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：16)；

His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：17)；

His-Ser-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：18)；

His-Thr-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：19)；

His-Leu-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：20)；

His-Ser-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Leu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：21)；

His-Ile-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：22)；

His-Leu-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Leu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：23)；

His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Leu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：24)；

His-Phe-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：25)；

His-Ile-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：26)；

His-Val-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：27)；

His-Lys-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Aia-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：28)；

His-D-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-NH₂(SEQ.ID NO：29)

His-D-Leu-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly-OH(SEQ.ID NO：30)；

His-Ser-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly-OH(SEQ.ID NO：31)

His-D-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly-OH(SEQ.ID NO：32)。