Synthesis and biological activity profile of new analogues of the cyclic opioid peptide H‐Tyr‐c[ D ‐Cys‐Gly‐Phe( p NO 2 )‐ D ‐Cys]‐NH 2 containing ( S )‐α‐hydroxymethylcysteine in place of cysteine

To examine the effect on biological activity of replacing D ‐Cys in the opioid peptide H‐Tyr‐c[ D ‐Cys‐Gly‐Phe( p NO 2 )‐ D ‐Cys]‐NH 2 in position 2 or/and 5 with α‐hydroxymethylcysteine (α‐Hmc), three analogues were synthesized. These compounds exhibit agonist activity at both µ and δ receptors. However, the most active analogue, with ( S )‐α‐Hmc residue in position 5, was 3360‐ and 2190‐fold less active than the parent peptide in the GPI and MVD assays, respectively. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.