1H n.m.r. investigation of conformational features of cyclic enkephalinamide analogs

The conformational basis for the differing opioid receptor selectivities of the cyclic cystine-containing analogs, [D-Cys2, D(or L)-Cys5] enkephalinamide and the related penicillamine-containing analogs, [D-Pen2, D(or L)-Cys5] enkephalinamide (penicillamine = beta, beta dimethylcysteine) was investigated by 1H n.m.r. in aqueous solution. Comparison of chemical shift, temperature dependence of amide proton chemical shift, and coupling constant data suggests similar overall conformations for corresponding penicillamine- and cystine-containing analogs. Differences in conformation and flexibility do appear in the carboxamide terminal region of the corresponding analogs, which may account for their selectivities for different classes of opioid receptors.