Dehydro-dermorphins. I. Influence of the stereo-orientation of aromatic groups in dermorphin-(1-5)-peptides to opioid activity.
Dehydrophenylalanine having the Z-configuration (delta Phe) and D-Phe were incorporated in positions 3 and/or 5 into dermorphin-(1-5)-peptide amide (H-Tyr-D-Ala-Phe-Gly-Tyr-NH2) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L-Phe5]-pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe3 by its D-enantiomer was barely tolerated. The pentapeptides containing delta Phe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to mu activity.
D000818:Animals; D006168:Guinea Pigs; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology; D018847:Opioid Peptides; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin