Homogeneous, Structurally Defined Heparin-Oligosaccharides With Low Anticoagulant Activity Inhibit the Generation of the Amplification Pathway C3 Convertase In Vitro
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Authors
Linhardt, Robert J.
Rice, K.G.
Kim, Y.S.
Engelken, J.
Weiler, J.
Issue Date
1988
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
This paper demonstrates that heparin-oligosaccharides with low anticoagulant activity have a high capacity to inhibit activation of the amplification pathway of complement in vitro. We prepared heparin-oligosaccharides by partial depolymerization of heparin using purified flavobacterial heparinase. The resulting oligosaccharide mixture was then fractionated using strong anion exchange-high pressure liquid chromatography to produce individual oligosaccharide components of this mixture, with degree of polymerization ranging from 2 to 16. These heparin-oligosaccharides were examined for both their anticoagulant activity and capacity to inhibit activation of the amplification pathway of complement. Although there was little difference among commercial heparins, a correlation between molecular weight and activity to inhibit convertase generation was clearly established for heparin-oligosaccharides between degree of polymerization 2 through 16. Heparin-oligosaccharides of degree of polymerization 10-16 (Mr 3888-5320) demonstrated up to 54% of heparin's activity on a molar basis (and up to 163% of heparin's activity on a weight basis) in inhibiting the amplification pathway of complement in vitro while showing almost no anticoagulant activity. These studies, for the first time, completely separate heparin's ability to inhibit complement activation from its anticoagulant activity.
Description
The Journal of Biological Chemistry, 263, 13090-13096
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Homogeneous, Structurally Defined Heparin-Oligosaccharides With Low Anticoagulant Activity Inhibit the Generation of the Amplification Pathway C3 Convertase In Vitro, R.J. Linhardt, K.G. Rice, Y.S. Kim, J. Engelken, J. Weiler, The Journal of Biological Chemistry, 263, 13090-13096 (1988).
Publisher
Elsevier