A gastrin-releasing peptide antagonist containing a ψ(CH 2O) amide bond surrogate

The [Leu 26-ψ(CH 2O)Leu 27] derivative of N-Ac-GRP20–27-peptide amide was prepared and evaluated as a gastrin-releasing peptide antagonist. This ψ(CH 2O) derivative was found to be a more potent inhibitor of [ 3H-Phe 15]GRP15–27NH 2 binding and N-Ac-GRP20–27NH 2 induced mitogenesis in Swiss 3T3 fibroblasts than the related nitrogen analog [Leu 13-ψ(CH 2NH)Leu 14]bombesin. Possible reasons for the improved activity of the (CH 2O) insert relative to the (CH 2NH) group include increased hydrophobicity and a reduced tendency of the oxygen derivative to form hydrogen bonds.