Synthesis and biological activities of position one and three transposed analogs of the opioid peptide YKFA

Tyr-c[D-Lys-Phe-Ala], YKFA, is a potent opioid peptide analog with subnanomolar IC50s toward mu and delta receptors. Transposing Phe and Tyr, a modification found to promote mu antagonist activity in opioid/somatostatin hybrids, gave surprisingly high mu agonist activities for several related analogs, considering the lack of a 1-position hydroxyl function.