Role of the conformational element in peptide-receptor interactions. Studies with cyclic opioid peptide analogs.

Abstract

Biological activity profiles of three different families of cyclic opioid peptide analogs are presented. It is illustrated that conformational constraints introduced through peptide cyclizations can have drastic effects on receptor affinity, selectivity and 'efficacy' ('intrinsic activity'). Conformational studies of cyclic opioid peptides by various physico-chemical techniques have been initiated and have already produced insight into the conformational requirements of the various opioid receptor types. On the basis of the results obtained, conformational restriction of opioid peptides may represent a first promising step towards the goal of developing peptide mimetics.