Optical molecular sensors for cytochrome P450 activity

摘要

The invention provides a compound, useful as an optical probe or sensor of the activity of at least one cytochrome P450 enzyme, and methods of using the compound to screen candidate drugs, and candidate drugs identified by these methods. The optical probe of the 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 C₁-C₂₀ alkyl, unsaturated C₁-C₂₀ alkenyl, unsaturated C₁-C₂₀ alkynyl, substituted saturated C₁-C₂₀ alkyl, substituted unsaturated C₁-C₂₀ alkenyl, substituted unsaturated C₁-C₂₀ alkynyl, C₁-C₂₀ cycloalkyl, C₁-C₂₀ cycloalkenyl, substituted saturated C₁-C₂₀ cycloalkyl, substituted unsaturated C₁-C₂₀ cycloalkenyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; L is selected from the group of (-OCR²H)_p-, wherein for each p, all R² are separately selected from the group consisting of a hydrogen atom, saturated C₁-C₂₀ alkyl, unsaturated C₁-C₂₀ alkenyl, unsaturated C₁-C₂₀ alkynyl, substituted saturated C₁-C₂₀ alkyl, substituted unsaturated C₁-C₂₀ alkenyl, substituted unsaturated C₁-C₂₀ alkynyl, C₁-C₂₀ cycloalkyl, C₁-C₂₀ cycloalkenyl, substituted saturated C₁-C₂₀ cycloalkyl, substituted unsaturated C₁-C₂₀ cycloalkenyl, 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 hydroxylate, phenol or phenoxide form that are different from the optical properties that arise from its ether form. Most preferably, p is one, R² is hydrogen, and Q is the ether form of a phenoxide fluorophore.