Structural Features of Dermatan Sulfates and their Relationship to Anticoagulant and Antithrombotic Activities

Authors
Linhardt, Robert J.
Al-Hakim, Ali
Jian, Liu
Hoppensteadt, Debra
Mascellani, Giuseppe
Bianchini, Pietro
Fareed, Jawed
ORCID
https://orcid.org/0000-0003-2219-5833
No Thumbnail Available
Other Contributors
Issue Date
1991-09-27
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
Full Citation
Structural Features of Dermatan Sulfates and their Relationship to Anticoagulant and Antithrombotic Activities, R.J. Linhardt, A. Al-Hakim, J. Liu, D. Hoppensteadt, J. Fareed, G. Mascellani, P. Bianchini, Biochemical Pharmacology, 42, 1609-1619 (1991).
Abstract
Dermatan sulfate is a polydisperse, microheterogeneous sufated copolymer of N-acetyl-D-galactopyranose and idopyranosyluronic acid that is currently under clinical investigation as a new antithrombotic agent. The structure and activity of two pairs of dermatan sulfates, isolated from bovine and porcine mucosa, were studied. One dermatan sulfate from each species demonstrated high in vivo antithrombotic activity in the rat vena cava assay. The in vitro anticoagulant activity of each dermatan sulfate was determined using activated partial thromboplastin time (APTT), thrombin time (TT) (5 units), calcium thrombin time (CaTT) (5 units), Heptest, anti-factor Xa and anti-factor IIa antithrombin assays and heparin cofactor II amidolytic assays. The coagulation-based assays gave the best correlation to in vivo antithrombotic activity. The physical and chemical properties of each dermatan sulfate were determined using 1H-NMR and 13C-NMR spectroscopy, molecular weight determination, potentiometric titration, chemical degradative analysis, chondroitin lyase degradative analysis and oligosaccharide mapping. These analyses indicated that the major difference between dermatan sulfates from a particular species having high and low in vivo antithrombotic activity was their iduronic acid content. The relation between increased iduronic acid content and increased in vivo antithrombotic activity may be the result of the conformational flexibility of this residue.
Description
Biochemical Pharmacology, 42, 1609-1619
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.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemical Pharmacology
https://harc.rpi.edu/
Access
https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/0006-2952(91)90431-4