Tryptophan-norleucine 1,5-disubstituted tetrazoles as cis peptide bond mimics: Investigation of the bioactive conformation of a potent and selective peptide for the cholecystokinin-B receptor

Conformational analysis of the CCK-B receptor selective peptide Gly-Trp-N-(Me)Nle-Aps-PheNH2 suggests the possibility of cis-trans isomerization about the Trp-N-(Me)Nle peptide bond. We have described the synthesis of the tryptophan-norleucine containing tetrazole dipeptide TrpΨ[CN4]Nle as a cis amide bond surrogate. The peptide Gly-TrpΨ[CN4]Nle-Asp-PheNH2 had low affinity to the CCK-B receptor. However, the intermediate Boc-TrpΨ[CN4]Nle-Asp-PheNH2 had considerable affinity to the CCK-A receptor.