Photoinactivation of the mu opioid receptor using a novel synthetic morphiceptin analog.
The benzophenone chromophore has been incorporated into a synthetic amino acid (p-benzoyl-L-phenylalanine; L-Bpa) to produce a chemically stable photoaffinity probe. L-Bpa was found to retain the photochemical reactivity of benzophenone. To test the utility of this synthetic amino acid as a photo-reactive probe for receptors, a tetrapeptide analog of morphiceptin was made as a model peptide in which the C-terminal prolinamide was replaced by L-Bpa amide. The affinity of the mu opioid receptor for this peptide is comparable to that for the parent compound, morphiceptin. Irradiation of the peptide-receptor complex reduced the subsequent binding of [3H]naloxone and virtually eliminated that of [3H]Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO). Binding studies with [3H]naloxone indicated that both the affinity and the capacity were reduced. Competition studies with [3H]D-Ala2-D-Leu5-enkephalin (DADLE) and naloxone indicated selective inactivation of a mu type opioid receptor.
Herblin
W F
WF
Medical Products Department, E.I. du Pont de Nemours and Company, Wilmington, DE 19898.
Kauer
J C
JC
Tam
S W
SW
D000345:Affinity Labels; D000818:Animals; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008027:Light; D009270:Naloxone / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism / Q000528:radiation effects*; D017450:Receptors, Opioid, mu
D000345:Affinity Labels; D004723:Endorphins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D010649:Phenylalanine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C028889:morphiceptin; C053764:benzoylphenylalanine