Dehydro-dermorphins

Dehydrophenylalanine having the Z-configuration (ΔPhe) 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 ΔPhe 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 μ activity.