Low molecular weight heparins: Structural differentiation by bidimensional nuclear magnetic resonance spectroscopy
Low molecular weight heparins: Structural differentiation by bidimensional nuclear magnetic resonance spectroscopy
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DOI：
10.1055/s-2007-982078
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发表时间：
2007-07-01
影响因子：
5.7
通讯作者：
Torri, Giangiacomo
中科院分区：
文献类型：
--
作者：
Guerrini, Marco;Guglieri, Sara;Torri, Giangiacomo
由于制造的不同，单个低分子肝素(LMWHs)表现出不同的药理和生化特征。生物特性与特定结构基序的关联是设计新的低分子肝素以及开发专有低分子肝素的仿制版本中的一大挑战。二维核磁共振(核磁共振)谱可以识别和定量低分子肝素制剂的结构特性。本文利用异核单量子相干光谱技术，对三种低分子肝素(依诺肝素、达特肝素和替扎肝素)的结构进行了研究。对属于母体肝素的相关残基以及每个解聚过程产生的次要残基进行了表征和定量。使用高灵敏度核磁共振波谱仪(600 MHz配备低温探头)可以准确地定量残留物，灵敏度优于1%至2%。
Individual low molecular weight heparins (LMWHs) exhibit distinct pharmacological and biochemical profiles because of manufacturing differences. Correlation of biological properties with particular structural motifs is a major challenge in the design of new LMWHs as well as in the development of generic versions of proprietary LMWHs. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy permits identification and quantification of structural peculiarities of LMWH preparations. In this article, heteronuclear single quantum coherence spectroscopy, previously used to determine variously substituted monosaccharide components of heparan sulfate (HS) and HS-like glycosaminoglycan mimics, has been applied to the structural characterization of three commercially available LMWHs (enoxaparin, dalteparin, and tinzaparin). Relevant residues belonging to the parent heparin, as well as minor residues generated by each depolymerization procedure, have been characterized and quantified. The use of a high-sensitivity NMR spectrometer (600 MHz equipped with cryoprobe) allowed the accurate quantification of residues with sensitivity better than 1 to 2%.