Crystal structure of biphalin sulfate: a multireceptor opioid peptide

Abstract

Biphalin is a dimeric opioid peptide, composed of two tetrapeptides connected 'tail-to-tail', that exhibits a high affinity for all three opioid receptor types (i.e. mu, delta and kappa). This study presents the X-ray crystal structure of biphalin sulfate and compares it to other opioids that interact with the same biological targets. Both halves of the molecule have a folded backbone conformation but differ significantly from one another. Residues 1-4 in biphalin, which compare well with the delta selective opioid peptide DADLE, fold into a random coil. Residues 5-8, which can be fit to the mu selective peptide D-TIPP-NH2, exhibit a fairly normal type III' beta bend. Biphalin also exhibits structural similarities with two naltrexone analogs, naltrexonazine and norbinaltorphamine, that are specific to mu and kappa receptor sites.