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

Org Lett. 2005 Jul 7;7(14):2953-6. doi: 10.1021/ol0509179.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dipeptides / chemistry
  • Fentanyl / analogs & derivatives*
  • Fentanyl / chemistry*
  • Fentanyl / pharmacology
  • Molecular Mimicry
  • Molecular Structure
  • Morphine / pharmacology
  • Peptides / chemistry*
  • Rats
  • Receptors, Opioid, mu / chemistry*

Substances

  • Dipeptides
  • Peptides
  • Receptors, Opioid, mu
  • tryptophyl-histidine
  • aspartyltyrosine
  • Morphine
  • Fentanyl