用于蛋白质生物可逆酯化的重氮化合物。

McGrath Nicholas A, Andersen Kristen A, Davis Amy K F, Lomax Jo E, Raines Ronald T

Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 USA.

Molecular & Cellular Pharmacology Graduate Training Program, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706 USA.

Chem Sci. 2015 Jan 1;6(1):752-755. doi: 10.1039/C4SC01768D.

A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chemical modification could enable the key advantages of prodrugs to be translated from small-molecules to proteins.

已表明重氮化合物可在水性环境中有效地将羧酸转化为酯。重氮化合物的碱性至关重要：碱性低不会引发反应，但碱性高会导致水解。这种反应活性扩展到蛋白质中的羧酸基团。随后生成的酯会被人类细胞酯酶水解，以再生蛋白质羧基。这种新的化学修饰模式能够使前药的关键优势从小分子转化到蛋白质上。