| 摘要 |
Analogs of glucagon-like peptide-2 (GLP-2), a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical and therapeutic use in treating disorders of the small bowel is described. The GLP-2 analog is characterised by intestinotrophic activity and which conforms to formula described below: R1-(Y1)m-X1-X2-X3-X4-Ser5, Phe6-Ser7-Asp8-(P1)-Leu14-Asp15-Asn16-Leu17-Ala18-X19-X20-Asp21-Phe22-(P2)-Trp25-Leu26-Ile27-Gln-28-Thr29-Lys30-(P3)-(Y2)n-R2 Wherein X1 is His or Tyr X2 is Ala or an Ala-replacement amino acid conferring on said analog resistance to DPP-IV enzyme X3 is Pro, HPro, Asp or Glu X4 is Gly or Ala P1 is Glu-X10-Asn-Thr-Ile or Tyr-Ser-Lys-Tyr X10 is Met or an oxidatively stable Met-replacement amino acid X19 is Ala or Thr X20 is Arg, Lys, His or Ala P2 is Ile-Asn, Ile-Ala or Val-Gln P3 is a covalent bond, or is Ile, Ile-Thr or Ile-Thr-Asp R1 is H or an N-terminal blocking group R2 is OH or a C-terminal blocking group Y1 is one or two basic amino acids selected from the group Arg, Lys and His Y2 is one or two basic amino acids selected from the group Arg, Lys and His m and n, independently, are 0 or 1 and wherein at least one of X1, X2, X3, X4, P1, X10, X19, X20, P2 and P3 is other than a wild type, mammalian GLP-2 residue
|
