abstract |
A GLP-1 analog that is GLP-1 (7-35) (SEQ ID No. 1) modified having the sequence of formula (I) ** Formula ** in which Xaa7 is L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, β-hydroxy-histidine, homohistidine, Nα-acetylhistidine, α-fluoromethyl-histidine, α-methyl-histidine, 3-pyridylalanine, 2-pyridylalanine or 4-pyridylalanine; Xaa8 is Ala, Gly, Val, Leu, Ile, Lys, Aib, (1-aminocyclopropyl) carboxylic acid, (1-aminocyclobutyl) carboxylic acid, (1-aminocyclopentyl) carboxylic acid, (1-aminocyclohexyl) carboxylic acid, ( 1-aminocycloheptyl) carboxylic or (1-aminocyclooctyl) carboxylic acid; Xaa9 is Glu or a derivative of Glu such as alpha, alpha-dimethyl-Glu; Xaa16 is Val or Leu; Xaa18 is Ser, Lys, Cys or Arg; Xaa20 is Leu, Lys or Cys; Xaa23 is Gln, Glu, Lys, Cys or Arg; Xaa24 is Ala or Asn; Xaa25 is Ala or Val; Xaa27 is Glu, Ala or Leu; Xaa30 is Ala, Glu, Lys, Arg or is absent; Xaa31 is Trp, Lys, Cys or is absent; Xaa33 is Val, Lys, Cys or is absent; Xaa34 is Lys, Glu, Asn, Arg, Cys or is absent; Xaa35 is Gly, Aib or is absent; R is amide or absent; provided that if Xaa30, Xaa31, Xaa32, Xaa33 or Xaa34 is absent then each amino acid residue in the 3 'direction is also absent; and where the GLP-1 analog has a total of 2, 3, 4, 5, 6, 7, 8 or 9 amino acid substitutions compared to GLP-1 (7-35). |