Synthesis of a Bisubstrate Analogue Targeting Estrogen Sulfotransferase
- 18 October 2002
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 68 (1) , 170-173
- https://doi.org/10.1021/jo0260443
Abstract
Sulfotransferases catalyze the transfer of a sulfuryl group from the eukaryotic sulfate donor 3‘-phosphoadenosine 5‘-phosphosulfate to an acceptor biomolecule. Sulfotransferases have been linked with several disease states, prompting our investigation of specific sulfotransferase inhibitors. Presented herein is the synthesis and evaluation of a bisubstrate analogue designed to inhibit estrogen sulfotransferase. The synthesis utilizes a novel, orthogonally protected 3‘-phosphoadenosine 5‘-phosphate (PAP) derivative allowing the selective functionalization of the 5‘-phosphate with a sulfate acceptor mimic. Kinetic studies revealed significant inhibitory activity and provide guidance for improved inhibitor design.Keywords
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