title: Trimethyl lock: a stable chromogenic substrate for esterases.
abstract: p-Nitrophenyl acetate is the most commonly used substrate for detecting the catalytic activity of esterases, including those that activate prodrugs in human cells. This substrate is unstable in aqueous solution, limiting its utility. Here, a stable chromogenic substrate for esterases is produced by the structural isolation of an acetyl ester and p-nitroaniline group using a trimethyl lock moiety. Upon ester hydrolysis, unfavorable steric interactions between the three methyl groups of this o-hydroxycinnamic acid derivative encourage rapid lactonization to form a hydrocoumarin and release p-nitroaniline. This "prochromophore" could find use in a variety of assays.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Levine
authors.forename: Luke D
authors.initials: LD
authors.lastname: Lavis
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D002863:Chromogenic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D013057:Spectrum Analysis; D013379:Substrate Specificity; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D002863:Chromogenic Compounds; D004950:Esterases