Opioid activity of 4-imidazolidinone positional analogues of Leu-Enkephalin.

Modulation of opioid activity was accomplished for analogues of Leu-enkephalin through incorporation of a 4-imidazolidinone moiety. The peptide backbone was constrained via a methylene bridge between two neighboring amides within its regular peptide sequence, which was expected to disrupt the secondary structure of the original molecule. Five positional analogues of Leu-enkephalin based on the same sequence and different location of the imidazolidinone-constrict were designed, synthesized, and examined for their affinity to micro-, delta- and kappa-opioid receptors.