Imperial College London
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ProfessorStuartHaslam

Faculty of Natural Sciences, Department of Life Sciences

Professor in Structural Glycobiology
 
 
 
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Contact

 

+44 (0)20 7594 5222s.haslam

 
 
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Location

 

101ASir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wang:2018:10.1016/j.chembiol.2018.09.012,
author = {Wang, S-S and Gao, X and Solar, VD and Yu, X and Antonopoulos, A and Friedman, AE and Matich, EK and Atilla-Gokcumen, GE and Nasirikenari, M and Lau, JT and Dell, A and Haslam, SM and Laine, RA and Matta, KL and Neelamegham, S},
doi = {10.1016/j.chembiol.2018.09.012},
journal = {Cell Chemical Biology},
pages = {1--14},
title = {Thioglycosides Are efficient metabolic decoys of glycosylation that reduce selectin dependent leukocyte adhesion},
url = {http://dx.doi.org/10.1016/j.chembiol.2018.09.012},
volume = {25},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Metabolic decoys are synthetic analogs of naturally occurring biosynthetic acceptors. These compounds divert cellular biosynthetic pathways by acting as artificial substrates that usurp the activity of natural enzymes. While O-linked glycosides are common, they are only partially effective even at millimolar concentrations. In contrast, we report that N-acetylglucosamine (GlcNAc) incorporated into various thioglycosides robustly truncate cell surface N- and O-linked glycan biosynthesis at 10-100 μM concentrations. The >10-fold greater inhibition is in part due to the resistance of thioglycosides to hydrolysis by intracellular hexosaminidases. The thioglycosides reduce β-galactose incorporation into lactosamine chains, cell surface sialyl Lewis-X expression, and leukocyte rolling on selectin substrates including inflamed endothelial cells under fluid shear. Treatment of granulocytes with thioglycosides prior to infusion into mouse inhibited neutrophil homing to sites of acute inflammation and bone marrow by ∼80%-90%. Overall, thioglycosides represent an easy to synthesize class of efficient metabolic inhibitors or decoys. They reduce N-/O-linked glycan biosynthesis and inflammatory leukocyte accumulation.
AU  - Wang,S-S
AU  - Gao,X
AU  - Solar,VD
AU  - Yu,X
AU  - Antonopoulos,A
AU  - Friedman,AE
AU  - Matich,EK
AU  - Atilla-Gokcumen,GE
AU  - Nasirikenari,M
AU  - Lau,JT
AU  - Dell,A
AU  - Haslam,SM
AU  - Laine,RA
AU  - Matta,KL
AU  - Neelamegham,S
DO  - 10.1016/j.chembiol.2018.09.012
EP  - 14
PY  - 2018///
SN  - 2451-9448
SP  - 1
TI  - Thioglycosides Are efficient metabolic decoys of glycosylation that reduce selectin dependent leukocyte adhesion
T2  - Cell Chemical Biology
UR  - http://dx.doi.org/10.1016/j.chembiol.2018.09.012
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30344053
UR  - http://hdl.handle.net/10044/1/65062
VL  - 25
ER  -
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