The invention provides methods of using a compound 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 kits for performing
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 C.sub.1 -C.sub.20 alkyl, unsaturated
C.sub.1 -C.sub.20 alkenyl, unsaturated C.sub.1 -C.sub.20 alkynyl,
substituted saturated C.sub.1 -C.sub.20 alkyl, substituted unsaturated
C.sub.1 -C.sub.20 alkenyl, substituted unsaturated C.sub.1 -C.sub.20
alkynyl, C.sub.1 -C.sub.20 cycloalkyl, C.sub.1 -C.sub.20 cycloalkenyl,
substituted saturated C.sub.1 -C.sub.20 cycloalkyl, substituted
unsaturated C.sub.1 -C.sub.20 cycloalkenyl, aryl, substituted aryl,
heteroaryl and substituted heteroaryl; L is selected from the group of
(--OCR.sup.2 H).sub.p --, wherein for each p, all R.sup.2 are separately
selected from the group consisting of a hydrogen atom, saturated C.sub.1
-C.sub.20 alkyl, unsaturated C.sub.1 -C.sub.20 alkenyl, unsaturated
C.sub.1 -C.sub.20 alkynyl, substituted saturated C.sub.1 -C.sub.20 alkyl,
substituted unsaturated C.sub.1 -C.sub.20 alkenyl, substituted unsaturated
C.sub.1 -C.sub.20 alkynyl, C.sub.1 -C.sub.20 cycloalkyl, C.sub.1 -C.sub.20
cycloalkenyl, substituted saturated C.sub.1 -C.sub.20 cycloalkyl,
substituted unsaturated C.sub.1 -C.sub.20 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 hyrdoxylate, phenol or phenoxide form that
are different from the optical properties that arise from its ether form.
Most preferably, p is one, R.sup.2 is hydrogen, and Q is the ether form of
a phenoxide fluorophore.
La invención proporciona métodos de usar un compuesto como una punta de prueba o sensor óptica de la actividad por lo menos de una enzima del cytochrome P450, y métodos de usar el compuesto para defender las drogas del candidato, y los kits para realizar estos métodos. La punta de prueba óptica de la invención es un compuesto que tiene la estructura genérica Y-L-Q, en donde Y se selecciona del grupo que consiste en Q como C.sub.1 adjunto definido, saturado - C.sub.20 alkyl, C.sub.1 no saturado - C.sub.1 alkenyl, no saturado de C.sub.20 - C.sub.20 alkynyl, C.sub.1 saturado substituido - el alkyl C.sub.20, C.sub.1 no saturado substituido - C.sub.20 alkenyl, C.sub.1 no saturado substituido - el alkynyl C.sub.20, C.sub.1 - C.sub.20 cycloalkyl, C.sub.1 - el cycloalkenyl C.sub.20, C.sub.1 saturado substituido - C.sub.20 cycloalkyl, C.sub.1 no saturado substituido - el cycloalkenyl C.sub.20, aryl, aryl substituido, heteroaryl y heteroaryl substituido; L se selecciona del grupo de (- - OCR.sup.2 H).sub.p --. en donde para cada p, todos los R.sup.2 se seleccionan por separado del grupo que consiste en un átomo del hidrógeno, C.sub.1 saturado - C.sub.20 alkyl, C.sub.1 no saturado - C.sub.20 alkenyl, C.sub.1 no saturado - C.sub.20 alkynyl, C.sub.1 saturado substituido - C.sub.20 alkyl, C.sub.1 no saturado substituido - C.sub.20 alkenyl, C.sub.1 no saturado substituido - C.sub.20 alkynyl, C.sub.1 - C.sub.20 cycloalkyl, C.sub.1 - cycloalkenyl C.sub.20, substituyó C.sub.1 saturado - C.sub.20 cycloalkyl, C.sub.1 no saturado substituido - el cycloalkenyl C.sub.20, el aryl, el aryl substituido, el heteroaryl, el heteroaryl substituido, y p es un número entero positivo no mayor que doce; y Q es un moiety químico que da lugar a características ópticas en su hydroxy o forma del hyrdoxylate, del fenol o del phenoxide que es diferente de las características ópticas que se presentan de su forma del éter. Preferiblemente, p es uno, R.sup.2 es hidrógeno, y Q es la forma del éter de un fluorophore del phenoxide.
