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

Abstract

The α‐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 Seyler371, 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 γ‐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 γ‐lactam structure (ii) repre..