DESIGN OF PEPTIDES AND PEPTIDOMIMETICS FOR DELTA-OPIOID AND KAPPA-OPIOID RECEPTOR SUBTYPES

Dynorphin A (1-17) and related compounds are putative endogenous ligan ds for kappa (kappa) opioid receptors, but they also are highly potent at mu (mu) and delta (delta) opioid receptors. Thus, they are excelle nt starting structures for the design of highly selective ligands for all opioid receptor types. Based on conformational, topographical and stereoelectronic considerations, we have designed a series of Dynorphi n A (1-11) analogues that are highly potent and selective for either t he delta or kappa or mu opioid receptors. We outline some structural a nd conformational features that distinguish kappa and delta receptor s elective Dynorphin analogues. Changes in the message and address regio n are important.