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Heptapeptide mimic of ohmefentanyl binding in the discontinuous mu-opiod receptor
Robert E Gawley1, Mykhaylo Dukh, Claudia M Cardona
1Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, 72701, USA. bgawley@uark.edu
Abstract:
[reaction: see text] Ohmefentanyl binds to the rat mu-opiod receptor via two dipeptide sequences (Trp-His and Asp-Tyr) that are separated by 170 residues. A turn-inducing tripeptide, Pro-Aib-Aib, holds the dipeptides in a conformation that binds the narcotic (K(b) = 7.1 x 10(4) M(-)(1)) in THF. Binding is specific for ohmefentanyl over morphine and is accompanied by a conformational change in the heptapeptide host. Control experiments with a Gly-Gly-Gly tripeptide linking the dipeptides show no evidence of binding.
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