부산대학교 도서관

The crystallographic structure of opioid receptors has been a great unknown until its recent discovery. This thesis has made contributions to the rational design of opioid drugs, by tuning proteomic analysis techniques on opioid receptors and studying their interactions with endogenous peptide ligands (enkephalins and endorphins) and its analogues to a better understanding of conformations of the ligands and their binding mode to the active center. Furthermore, studies have been made about new inhibitors of enzymes which degrade enkephalins (NEP and aminopeptidase-N). Opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH) exhibits potent analgesic activity in animal models of pain after chemical and mechanical stimulation equipotent to morphine, by activation of the endogenous opioid system. It is secreted in human saliva and acts as a dual inhibitor of NEP and AP-N. In this part, structure-activity relationship (SAR) and conformational studies have been made to improve the design of inhibitors of these enzymes.