Heptapeptide mimic of ohmefentanyl binding in the discontinuous mu-opiod receptor.
[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.
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, 72701, USA. bgawley@uark.edu
Robert E
RE
Gawley
Mykhaylo
M
Dukh
Claudia M
CM
Cardona
Stephan H
SH
Jannach
Denise
D
Greathouse
D000595:Amino Acid Sequence; D000818:Animals; D004151:Dipeptides / Q000737:chemistry; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D018716:Molecular Mimicry; D015394:Molecular Structure; D009020:Morphine / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000737:chemistry*
D004151:Dipeptides; D010455:Peptides; D017450:Receptors, Opioid, mu; C509582:tryptophyl-histidine; C078779:aspartyltyrosine; D009020:Morphine; D005283:Fentanyl