Synthesis and receptor binding of opioid peptide analogues containing β³‐<i>homo</i>‐amino acids

Abstract

beta-Amino acids containing hybrid peptides and beta-peptides show great potential as peptidomimetics. In this paper we describe the synthesis and affinity toward the micro- and delta-opioid receptors of beta-peptides, analogues of Leu-enkephalin, deltorphin I, dermorphin and alpha,beta-hybrides, analogues of deltorphin I. Substitution of alpha-amino acid residues with beta(3)-homo-amino acid residues, in general resulted in decrease of affinity to opioid receptors. However, the incorporation beta(3)h-D-Ala in position 2 or beta(3)hPhe in position 3 of deltorphin I resulted in potent and selective ligand for delta-opioid receptor. The NMR studies of beta-deltorphin I analogue suggest that conformational motions in the central part of the peptide backbone are partially restricted and some conformational preferences can be expected.