Synthesis and Characterization of an Anomeric Sulfur Analogue of CMP-Sialic Acid

Abstract
α-2,3-Sialyltransferase catalyzes the transfer of sialic acid from CMP-sialic acid (1) to a lactose acceptor. An analogue of 1 was synthesized in which the anomeric oxygen atom was replaced with a sulfur atom (1 S). The key step in the synthesis of 1 S was a tetrazole-promoted coupling of a cytidine-5‘-phosphoramidite with a glycosyl thiol of a protected sialic acid. Compounds 1 and 1 S were characterized for their activity in a sialyl transfer assay. The rate of solvolysis in aqueous buffer of analogue 1 S was 50-fold slower than that of 1. Analogue 1 S was found to be substrate for α-2,3-sialyltransferase. The Km of 1 S was just 3-fold higher than that of 1, while the kcat of 1 S was 2 orders of magnitude lower compared to 1.

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