Convergent Synthesis of Sialyl Lewis(x)-O-Core-1 Threonine

Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P...

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Published inJournal of organic chemistry Vol. 83; no. 9; pp. 4963 - 4972
Main Authors Sardar, Mohammed Y. R., Mandhapati, Appi Reddy, Park, Simon, Weyer, Walter J., Cummings, Richard D., Chaikof, Elliot L.
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 04.05.2018
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
N-ACETYLGLUCOSAMINE
SELECTIN GLYCOPROTEIN LIGAND-1
IN-VITRO
LEUKOCYTE RECRUITMENT
TYROSINE SULFATE
LEWIS-X TETRASACCHARIDE
P-SELECTIN
GLYCOSYLATION
O-SIALYLATION
BINDING
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Summary:Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl Lewis(X) (sLe(X)) linked to a Core-1-O-hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using alpha-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.
Bibliography:NIH RePORTER
ISSN:0022-3263
DOI:10.1021/acs.joc.7b03117