Ultra-low-molecular-weight heparins: Precise structural features impacting specific anticoagulant activities

Ultra-low-molecular-weight heparins: Precise structural features impacting specific anticoagulant activities

Author Lima, Marcelo A. Autor UNIFESP Google Scholar
Viskov, Christian Google Scholar
Herman, Frederic Google Scholar
Gray, Angel L. Google Scholar
Farias, Eduardo H. C. de Autor UNIFESP Google Scholar
Cavalheiro, Renan P. Autor UNIFESP Google Scholar
Sassaki, Guilherme L. Google Scholar
Hoppensteadt, Debra Google Scholar
Fareed, Jawed Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Liverpool
Sanofi Rech
Loyola Univ
Univ Fed Parana
Abstract Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. the main structural features and molecular weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weights were determined and preparations studied by nuclear magnetic resonance spectroscopy, scanning ultraviolet spectroscopy, circular dichroism and gel permeation chromatography. in general, ULMWHs presented higher 3-O-sulphated glucosamine and unsaturated uronic acid residues, the latter being comparable with their higher degree of depolymerisation. the analysis showed that ULMWHs are structurally related to LMWHs; however, their monosaccharide/oligosaccharide compositions and average molecular weights differed considerably explaining their different anticoagulant activities. the results relate structural features to activity, assisting the development of new and improved therapeutic agents, based on depolymerised heparin, for the prophylaxis and treatment of thrombotic disorders.
Keywords Heparin
enoxaparin
molecular weight
spectroscopy
anticoagulant activity
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2013-03-01
Published in Thrombosis and Haemostasis. Stuttgart: Schattauer Gmbh-verlag Medizin Naturwissenschaften, v. 109, n. 3, p. 471-478, 2013.
ISSN 0340-6245 (Sherpa/Romeo, impact factor)
Publisher Schattauer Gmbh-verlag Medizin Naturwissenschaften
Extent 471-478
Origin http://dx.doi.org/10.1160/TH12-11-0795
Access rights Closed access
Type Article
Web of Science ID WOS:000316164200016
URI http://repositorio.unifesp.br/handle/11600/36066

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