Synthesis of a bisubstrate analogue targeting estrogen sulfotransferase

Article abstract of DOI:10.1021/jo0260443

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.