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

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 μM) than the parent disacchari...

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Bibliographic Details
Published in:Journal of organic chemistry 2000-04, Vol.65 (8), p.2393-2398
Main Authors: Shibata, Kayoko, Hiruma, Kazumi, Kanie, Osamu, Wong, Chi-Huey
Format: Article
Language:English
Subjects:
Carbohydrate Sequence
Magnetic Resonance Spectroscopy
Mannosides - chemical synthesis
Molecular Sequence Data
Oligosaccharides - chemical synthesis
P-Selectin - chemistry
Polysaccharides - chemical synthesis
Thiazines - chemical synthesis
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Summary: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 μM) than the parent disaccharide 2, which contains a flexible carboxyl group (IC50 = 193 μM). 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.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo991556b