Synthesis of 1,1-linked galactosyl mannosides carrying a thiazine ring as mimetics of sialyl lewis x antigen: Investigation of the effect of carboxyl group orientation on p-selectin inhibition

Academic Article
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publication date

  • 2000

abstract

  • This paper describes the synthesis of 1,1-linked galactosyl mannosides as sialyl Lewis X mimetics that contain a spiro-ring to position the carboxylate group in a well-defined orientation. It was found that compound 4 is more active as a P-selectin inhibitor (IC50 = 19 microM) than the parent disaccharide 2, which contains a flexible carboxyl group (IC50 = 193 microM). This result is consistent with that observed in the previous NMR study of sialyl Lewis X bound to P-selectin. The chemistry described here should be useful for the development of selective inhibitors of E-, P-, and L-selectins.