Heptapeptide mimic of ohmefentanyl binding in the discontinuous mu-opiod receptor

by Gawley, R. E.; Dukh, M.; Cardona, C. M.; Jannach, S. H.; Greathouse, D.

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.

Journal
Organic Letters
Volume
7
Issue
14
Year
2005
Start Page
2953-2956
URL
https://dx.doi.org/10.1021/ol0509179
ISBN/ISSN
1523-7052; 1523-7060
DOI
10.1021/ol0509179