Structure-activity relationship of endomorphins and their analogs

To study the structure-activity relationship of endomorphins (EMs), the action of opioid receptor binding (AORB), analgesic activity and vasodilator effects of EMs and their eight analogs were investigated, which were prepared by rationally replacing the 2-/3-amino acid (Aa) of EMs. The results showed: i) The 2-Aa was comparatively more related to the selectivity of EMs while the 3-Aa to their affinity; ii) the analgesia and vasodilatation of EMs and their analogs were not completely dictated by their AORB (in vitro), the action of D-Pro²]EM-2 was unusual; iii) EMs lost their analgesia in the central nervous system and their vasodilatation in the circulatory system with different mechanisms; the former was due to the degradation of some peptidase, and the latter possibly due to the feedback inhibition.