Synthesis and characterization of an anomeric sulfur analogue of CMP-sialic acid

被引:35
作者
Cohen, SB [1 ]
Halcomb, RL [1 ]
机构
[1] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA
关键词
D O I
10.1021/jo000646+
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
alpha-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 (1S). The key step in the synthesis of 1S was a tetrazole-promoted coupling of a cytidine-5'-phosphoramidite with a glycosyl thiol of a protected sialic acid. Compounds 1 and 1S were characterized for their activity in a sialyl transfer assay. The rate of solvolysis in aqueous buffer of analogue 1S was 50-fold slower than that of 1. Analogue 1S was found to be substrate for alpha-2,3-sialyltransferase. The K-m of 1S was just 3-fold higher than that of 1, while the k(cat) of 1S was 2 orders of magnitude lower compared to 1.
引用
收藏
页码:6145 / 6152
页数:8
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