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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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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cited_by cdi_FETCH-LOGICAL-a349t-7e4222c03bf4008e0954a22d287b9802050926a796e6337f49a0b36a0f742b323
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container_title Journal of organic chemistry
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creator Shibata, Kayoko
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Kanie, Osamu
Wong, Chi-Huey
description 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.
doi_str_mv 10.1021/jo991556b
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source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)
subjects Carbohydrate Sequence
Magnetic Resonance Spectroscopy
Mannosides - chemical synthesis
Molecular Sequence Data
Oligosaccharides - chemical synthesis
P-Selectin - chemistry
Polysaccharides - chemical synthesis
Thiazines - chemical synthesis
title 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
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