| 主权项 |
1. A glucagon derivative comprising an amino acid sequence of Formula I:
X1-X2-X3-Gly-Thr-Phe-Thr-Ser-Asp-X10-Ser-X12-Tyr-Leu-X15-X16-X17-X18-Ala-X20-X21-Phe-Val-X24-Trp-Leu-Ile-X28-X29-X30 (I) wherein X1 represents His or Imp; X2 represents Aib or Acb; X3 represents Gln or His; X10 represents Tyr, Leu, Ile or Val; X12 represents Lys or Arg; X15 represents Asp or Glu; X16 represents Ser, Ala, Leu, Thr, Glu, Aib, Ile, Val or Lys; X17 represents Arg, Lys or Gln; X18 represents Arg, Ala or Lys; X20 represents Gln, Arg or Lys; X21 represents Asp, Glu or Lys; X24 represents Gln, Ala, Arg, Glu or Lys; X28 represents Asn, Ser, Thr, Gln, Ala, Gly, Glu or Lys; X29 represents Thr, Gly, Ser, Gln, Ala, Glu or Lys; and X30 is absent or represents Lys; wherein said amino acid sequence of Formula I comprises a lysine residue at one or more of positions 12, 16, 17, 18, 20, 21, 24, 28, 29, and/or 30; and wherein said glucagon derivative comprises a substituent comprising a lipophilic moiety and at least three negatively charged moieties, wherein one of said negatively charged moieties is distal of a lipophilic moiety, and wherein said substituent is attached at the epsilon position of a lysine residue in one of the amino acid positions 16, 17, 18, 20, 21, 24, 28, 29 or 30; and wherein said glucagon derivative is a C-terminal amide; or a pharmaceutically acceptable salt thereof. |
