Methods for detecting the interaction of compounds with cytochrome p450 using optical molecular sensors

Abstract

The invention provides methods of using an optical molecular probe or sensor to screen candidate drugs for their interaction with at least one cytochrome P450 enzyme. The optical molecular probe useful in the methods of the present invention is a compound having the generic structure Y-L-Q, wherein Y is selected from the group consisting of Q as herein defined, saturated C–Calkyl, unsaturated C–Calkenyl, unsaturated C–Calkynyl, substituted saturated C–Calkyl, substituted unsaturated C–Calkenyl, substituted unsaturated C–Calkynyl, C–Ccycloalkyl, C–Ccycloalkenyl, substituted saturated C–Ccycloalkyl, substituted unsaturated C–Ccycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (—OCRH)—, wherein for each p, all Rare separately selected from the group consisting of a hydrogen atom, saturated C–Calkyl, unsaturated C–Calkenyl, unsaturated C–Calkynyl, substituted saturated C–Calkyl, substituted unsaturated C–Calkenyl, substituted unsaturated C–Calkynyl, C–Ccycloalkyl, C–Ccycloalkenyl, substituted saturated C–Ccycloalkyl, substituted unsaturated C–Ccycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and p is a positive integer no greater than twelve; and Q is a chemical moiety that gives rise to optical properties in its hydroxy or hyrdoxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, Ris hydrogen, and Q is the ether form of a phenoxide fluorophore.