Heparin mapping using heparin lyases and the generation of a novel low molecular weight heparin
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Authors
Xiao, Zhongping
Tappen, Britney R.
Ly, Mellisa
Zhao, Wenjing
Canova, Lauren P.
Guan, Huashi
Linhardt, Robert J.
Issue Date
2011-01-27
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Seven pharmaceutical heparins were investigated by oligosaccharide mapping by digestion with heparin lyase 1, 2, or 3, followed by high performance liquid chromatography analysis. The structure of one of the prepared mapping standards, ΔUA-Gal-Gal-Xyl-O-CH(2)CONHCH(2)COOH (where ΔUA is 4-deoxy-α-l-threo-hex-4-eno-pyranosyluronic acid, Gal is β-d-galactpyranose, and Xyl is β-d-xylopyranose) released from the linkage region using either heparin lyase 2 or heparin lyase 3 digestion, is reported for the first time. A size-dependent susceptibility of site cleaved by heparin lyase 3 was also observed. Heparin lyase 3 acts on the undersulfated domains of the heparin chain and does not cleave the linkages within heparin's antithrombin III binding site. Thus, a novel low molecular weight heparin (LMWH) is afforded on heparin lyase 3 digestion of heparin due to this unique substrate specificity, which has anticoagulant activity comparable to that of currently available LMWH.
Description
Journal of Medicinal Chemistry, 54, 603–610
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
Heparin mapping using heparin lyases and the generation of a novel low molecular weight heparin, Z. Xiao, B. R. Tappen, M. Ly, W. Zhao, L. P. Canova, H. Guan, R. J. Linhardt, Journal of Medicinal Chemistry, 54, 603–610, 2011. 2011.
Publisher
American Chemical Society (ACS)
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
15204804
222623
222623