Synthesis, biological activity and structure-activity relationship of endomorphin-1/substance P derivatives

A series of endomorphin-1/substance P (SP) hybrid peptides were synthesized with/without a 10-carbon lipoamino acid (C10LAA) modification. In vitro biological analyses revealed that the C10LAA-modified analogue conjugated with the SP7-11 fragment was the most promising derivative. This stable and permeable compound produced potent biological activity at μ-opioid receptors with selectivity over δ-opioid receptors, similar to that of endomorphin-1.