Structure-activity relationship of the novel bivalent and C-terminal modified analogues of endomorphin-2

Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) is a putative endogenous p-opioid receptor ligand. To develop potent analgesics with less side effects related to it, we used the methods of dimerization and C-terminal modification. Through dimerization we got the 'balanced agonists' with potent analgesic activity and we have developed the structure-activity relationship between the selectivity and the distance of the two tyrosine pharmacophores. Modification at the C-terminal increased the selectivity of endomorphin-2 to mu-opioid receptor with binding affinity conserved. (c) 2005 Elsevier Ltd. All rights reserved.