title: Low molecular weight heparins: structural differentiation by bidimensional nuclear magnetic resonance spectroscopy.
abstract: 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%.
authors.affiliation: Institute for Chemical and Biochemical Research G. Ronzoni, Via G. Colombo 81, 20133 Milan, Italy. guerrini@ronzoni.it
authors.forename: Marco
authors.initials: M
authors.lastname: Guerrini
authors.forename: Sara
authors.initials: S
authors.lastname: Guglieri
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.forename: Ram
authors.initials: R
authors.lastname: Sasisekharan
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
mesh_terms: D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012680:Sensitivity and Specificity
chemical_list: D006495:Heparin, Low-Molecular-Weight