The effect of increasing the sulfation level of chondroitin sulfate on anticoagulant specific activity and activation of the kinin system

PloS One
J HogwoodE Gray

Abstract

Oversulfated chondroitin sulfate (OSCS) was identified as a contaminant in certain heparin preparations as the cause of adverse reactions in patients. OSCS was found to possess both plasma anticoagulant activity and the ability to activate prekallikrein to kallikrein. Differentially sulfated chondroitin sulfates were prepared by synthetic modification of chondroitin sulfate and were compared to the activity of OSCS purified from contaminated heparin. Whilst chondroitin sulfate was found to have minimal anticoagulant activity, increasing sulfation levels produced an anticoagulant response which we directly show for the first time is mediated through heparin cofactor II. However, the tetra-sulfated preparations did not possess any higher anticoagulant activity than several tri-sulfated variants, and also had lower heparin cofactor II mediated activity. Activation of prekallikrein was concentration dependent for all samples, and broadly increased with the degree of sulfation, though the di-sulfated preparation was able to form more kallikrein than some of the tri-sulfated preparations. The ability of the samples to activate the kinin system, as measured by bradykinin, was observed to be through kallikrein generation. These results...Continue Reading

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Citations

Feb 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariana I NevesCristina C Barrias
Feb 26, 2019·Frontiers in Medicine·Eduardo VilanovaPaulo A S Mourão
Jan 31, 2020·Neural Regeneration Research·Courtney J Mycroft-WestMark Andrew Skidmore
Aug 4, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vitor H PominBarbara Mulloy
Jan 13, 2021·Biomaterials Science·Jonathan DoroginMarian H Hettiaratchi
Dec 29, 2020·Phytotherapy Research : PTR·Gangliang Huang, Shiyu Huang
Feb 8, 2021·Drug Discovery Today·Sarita Mishra, Munia Ganguli
Apr 10, 2021·The Journal of Allergy and Clinical Immunology·Pierre Bruhns, Sylvie Chollet-Martin
May 1, 2021·Marine Drugs·Courtney J Mycroft-WestMark A Skidmore

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Methods Mentioned

BETA
fluorescence titration assay
ELISA
light-scattering
Assay
NMR
surface plasmon resonance

Software Mentioned

XWINNMR
CombiStats

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