Disciplina de Biologia Molecular, Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, 04044-020, Brazil.
Thromb Haemost. 2013 Mar;109(3):471-8. doi: 10.1160/TH12-11-0795. Epub 2013 Jan 17.
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.
正在开发具有更好疗效和安全性比的超低分子量肝素 (ULMWHs)；然而，可用的结构数据很少。研究并比较了 ULMWHs 的主要结构特征和分子量与依诺肝素。通过核磁共振波谱、扫描紫外光谱、圆二色性和凝胶渗透色谱法测定了它们的单糖组成和平均分子量，并对制剂进行了研究。一般来说，ULMWHs 具有更高的 3-O-硫酸化葡萄糖胺和不饱和糖醛酸残基，后者与其更高的解聚程度相当。分析表明，ULMWHs 与 LMWHs 在结构上有关；然而，它们的单糖/寡糖组成和平均分子量有很大差异，这解释了它们不同的抗凝活性。这些结果将结构特征与活性联系起来，有助于基于解聚肝素开发新的和改进的治疗剂，用于预防和治疗血栓性疾病。
