Capturing a sulfenic acid with arylboronic acids and benzoxaborole.
Post-translational redox generation of cysteine-sulfenic acids (Cys-SOH) functions as an important reversible regulatory mechanism for many biological functions, such as signal transduction, balancing cellular redox states, catalysis, and gene transcription. Herein we show that arylboronic acids and cyclic benzoxaboroles can form adducts with sulfenic acids in aqueous medium and that these boron-based compounds can potentially be used to trap biologically significant sulfenic acids. As proof of principle we demonstrate that a benzoxaborole can inhibit the enzyme activity of an iron-containing nitrile hydratase, which requires a catalytic αCys114-SOH in the active site. The nature of the adduct and the effect of the boronic acid's pK(a)(B) on the stability constant of the adduct are discussed within.
Department of Chemistry, Pennsylvania State University , University Park, Pennsylvania 16802, United States.
C Tony
CT
Liu
Stephen J
SJ
Benkovic
D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology; D001897:Boronic Acids / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D012240:Rhodococcus / Q000201:enzymology; D013434:Sulfenic Acids / Q000737:chemistry*
D001555:Benzene Derivatives; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D013434:Sulfenic Acids; D006836:Hydro-Lyases; C048831:nitrile hydratase