Synthesis and conformation of constrained peptides with hypoglycaemic activity derived from human growth hormone.

Abstract

The alpha-aminosuccinimide (Asu11) octapeptide analogue of human growth hormone hGH[6-13] (Leu6-Ser-Arg-Leu-Phe-Asu-Asn-Ala13) has been reported [Robson et al. (1990) Biol. Chem. Hoppe Seyler 371, 423-431] to have hypoglycaemic activity whilst the corresponding peptide with Asp at position 11 is inactive. In order to determine whether this change in activity is caused by conformational and/or stereo-electronic effects, the incorporation of two different isomeric gamma-lactam structures at position 11 has been investigated. One lactam structure (i) is of the type developed by Freidinger and coworkers [Freidinger et al. (1982) J. Org. Chem. 47, 102-107], whilst the isomeric gamma-lactam struct..