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Chem Sci. 2015 Jan 1;6(1):752-755.

Diazo compounds for the bioreversible esterification of proteins.

Author information

1
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 USA.
2
Molecular & Cellular Pharmacology Graduate Training Program, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706 USA.
3
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706 USA.
4
Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706 USA.
5
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 USA ; Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706 USA.

Abstract

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.

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