Imperial College London

DrBarbaraMulloy

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

b.mulloy Website

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Panagos:2014:10.1074/jbc.M114.572297,
author = {Panagos, CG and Thomson, DS and Moss, C and Hughes, AD and Kelly, MS and Liu, Y and Chai, W and Venkatasamy, R and Spina, D and Page, CP and Hogwood, J and Woods, RJ and Mulloy, B and Bavington, CD and Uhrin, D},
doi = {10.1074/jbc.M114.572297},
journal = {Journal of Biological Chemistry},
pages = {28284--28298},
title = {Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali CONFORMATION, SELECTIN BINDING, AND BIOLOGICAL ACTIVITY},
url = {http://dx.doi.org/10.1074/jbc.M114.572297},
volume = {289},
year = {2014}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali is composed of the following repeating trisaccharide unit: →3)GalNAcβ4,6S(1→4) [FucαX(1→3)]GlcAβ(1→, where X stands for different sulfation patterns of fucose (X = 3,4S (46%), 2,4S (39%), and 4S (15%)). As revealed by NMR and molecular dynamics simulations, the fCS repeating unit adopts a conformation similar to that of the Lex blood group determinant, bringing several sulfate groups into close proximity and creating large negative patches distributed along the helical skeleton of the CS backbone. This may explain the high affinity of fCS oligosaccharides for L- and P-selectins as determined by microarray binding of fCS oligosaccharides prepared by Cu2+-catalyzed Fenton-type and photochemical depolymerization. No binding to E-selectin was observed. fCS poly- and oligosaccharides display low cytotoxicity in vitro, inhibit human neutrophil elastase activity, and inhibit the migration of neutrophils through an endothelial cell layer in vitro. Although the polysaccharide showed some anti-coagulant activity, small oligosaccharide fCS fragments had much reduced anticoagulant properties, with activity mainly via heparin cofactor II. The fCS polysaccharides showed prekallikrein activation comparable with dextran sulfate, whereas the fCS oligosaccharides caused almost no effect. The H. forskali fCS oligosaccharides were also tested in a mouse peritoneal inflammation model, where they caused a reduction in neutrophil infiltration. Overall, the data presented support the action of fCS as an inhibitor of selectin interactions, which play vital roles in inflammation and metastasis progression. Future studies of fCS-selectin interaction using fCS fragments or their mimetics may open new avenues for therapeutic intervention.
AU - Panagos,CG
AU - Thomson,DS
AU - Moss,C
AU - Hughes,AD
AU - Kelly,MS
AU - Liu,Y
AU - Chai,W
AU - Venkatasamy,R
AU - Spina,D
AU - Page,CP
AU - Hogwood,J
AU - Woods,RJ
AU - Mulloy,B
AU - Bavington,CD
AU - Uhrin,D
DO - 10.1074/jbc.M114.572297
EP - 28298
PY - 2014///
SN - 0021-9258
SP - 28284
TI - Fucosylated Chondroitin Sulfates from the Body Wall of the Sea Cucumber Holothuria forskali CONFORMATION, SELECTIN BINDING, AND BIOLOGICAL ACTIVITY
T2 - Journal of Biological Chemistry
UR - http://dx.doi.org/10.1074/jbc.M114.572297
UR - http://hdl.handle.net/10044/1/55270
VL - 289
ER -