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

2013 ◽  
Vol 109 (03) ◽  
pp. 471-478 ◽  
Author(s):  
Marcelo Lima ◽  
Christian Viskov ◽  
Frederic Herman ◽  
Angel Gray ◽  
Eduardo de Farias ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Gel Permeation Chromatography ◽  
Structural Data ◽  
Monosaccharide Composition ◽  
Structural Features ◽  
Therapeutic Agents ◽  
Resonance Spectroscopy ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Molecular Weights

SummaryUltra-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.

Molecular Weight Measurements of Low Molecular Weight Heparins by Gel Permeation Chromatography

1997 ◽  
Vol 77 (04) ◽  
pp. 668-674 ◽  
Author(s):  
B Mulloy ◽  
C Gee ◽  
S F Wheeler ◽  
R Wait ◽  
E Gray ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
High Performance ◽  
Gel Permeation Chromatography ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Molecular Weights ◽  
Calibration Table ◽  
Gel Permeation ◽  
Degraded Material

SummaryThe molecular weight profiles of low molecular weight heparin samples have been measured by high-performance gel permeation chromatography using as calibrant the heparinase-degraded material (90/686) now established as the 1st International Reference Preparation (IRP) Low Molecular Weight Heparin for Molecular Weight Calibration. Use of the calibrant as a broad molecular weight standard is described and a calibration table provided based on data collected over several years in one laboratory.In order to confirm the assignment of degree of polymerisation to resolved oligosaccharide peaks in the calibrant, molecular weights of oligosaccharides fractionated from the 1st IRP were independently determined by fast atom bombardment mass spectrometry (FAB MS).The molecular weight distributions of commercial low molecular weight heparins have been characterized. Measurements of molecular weight parameters of heparin molecular weight standards from several sources provide comparisons between the molecular weight scales of this and other studies.

Structural features of low-molecular-weight heparins affecting their affinity to antithrombin

2009 ◽  
Vol 102 (11) ◽  
pp. 865-873 ◽  
Author(s):  
Antonella Bisio ◽  
Davide Vecchietti ◽  
Laura Citterio ◽  
Marco Guerrini ◽  
Rahul Raman ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Nmr Spectra ◽  
Biological Activities ◽  
Anticoagulant Activity ◽  
2D Nmr ◽  
Structural Features ◽  
Size Exclusion ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
2D Nmr Spectra

SummaryAs part of a more extensive investigation on structural features of different low-molecular-weight heparins (LMWHs) that can affect their biological activities, Enoxaparin,Tinzaparin and Dalteparin were characterised with regards to the distribution of different chain length oligosaccharides as determined by size-exclusion (SE) chromatography, as well as their structure as defined by 2D-NMR spectra (HSQC). The three LMWHs were also fractionated into high affinity (HA) and no affinity (NA) pools with regards to their ability to bind antithrombin (AT).The HA fractions were further subfractionated and characterised. For the parent LMWHs and selected fractions,molecular weight parameters were measured using a SE chromatographic system with a triple detector (TDA) to obtain absolute molecular weights. The SE chromatograms clearly indicate that Enoxaparin is consistently richer in shorter oligosaccharides than Tinzaparin and Dalteparin. Besides providing the content of terminal groups and individual glucosamine and uronic acid residues with different sulfate substituents, the HSQC-NMR spectra permitted us to evaluate and correlate the content of the pentasaccharide, AT-binding sequence A-G-A*-I-A (AT-bs) through quantification of signals of the disaccharide sequence G-A*.Whereas the percent content of HA species is approximately the same for the three LMWHs, substantial differences were observed for the chain distribution of AT-bs as a function of length, with the AT-bs being preferentially contained in the longest chains of each LMWH. The above information will be useful in establishing structure-activity relationships currently under way. This study is therefore critical for establishing correlations between structural features of LMWHs and their AT-mediated anticoagulant activity.

Comparison of Number—Average Molecular Weights Calculated by GPC and Membrane Osmometry

1973 ◽  
Vol 46 (1) ◽  
pp. 115-126
Author(s):  
M. R. Ambler ◽  
R. D. Mate
Keyword(s):  
Molecular Weight ◽  
Gel Permeation Chromatography ◽  
Appreciable Amount ◽  
Diffusion Limit ◽  
Low Molecular Weight ◽  
Molecular Weights ◽  
True Value ◽  
Usual Manner ◽  
Gel Permeation ◽  
Polymer Species

Abstract Data are presented which show that when a polymer contains an appreciable amount of low molecular weight species below the diffusion limit of the osmometer membrane, the osmotic molecular weight, Mn, is generally higher than the Mn calculated from gel-permeation chromatography (GPC). Experiments were performed on samples of poly(vinylchloride) (PVC) and high-cis poly (butadiene) polymers. Osmotic data were obtained in the usual manner, while GPC data were obtained using the universal calibration approach. It was found that when all polymer species below approximately 10,000 molecular weight were excluded from the calculation of Mn by GPC, agreement in Mn was obtained between membrane osmometry and GPC. The data obtained suggest that the choice of Mn as measured by membrane osmometry in the calibration of the GPC should not be done casually, as the measured Mn may not reflect the “true” value of that sample, especially when the polymer sample contains an appreciable amount of low molecular weight material.

scholarly journals Synthesis, structure and thermogravimetric analysis of α,ω-telechelic polydimethylsiloxanes of low molecular weight

2017 ◽  
Vol 82 (12) ◽  
pp. 1395-1416 ◽  
Author(s):  
Aleksandra Tasic ◽  
Marija Pergal ◽  
Malisa Antic ◽  
Vesna Antic
Keyword(s):  
Molecular Weight ◽  
Thermogravimetric Analysis ◽  
Degradation Mechanism ◽  
Gel Permeation Chromatography ◽  
Polymer Chains ◽  
Low Molecular Weight ◽  
Dilute Solution ◽  
Molecular Weights ◽  
Dilute Solution Viscometry

A series of ?,?-telechelic polydimethylsiloxanes (PDMS), with predetermined molecular weights of about 2500 g mol-1, was synthesized by siloxane equilibration reaction. Syntheses were performed using octamethylcyclotetrasiloxane (D4) and various disiloxanes: hexamethyldisiloxane (HMDS), 1,1,3,3-tetramethyldisiloxane (TMDS), 1,3-divinyltetramethyldisiloxane (DVTMDS), 1,3-bis(3-carboxypropyl)tetramethyldisiloxane (DCPTMDS) and 1,3-bis(3-aminopropyl)tetramethyldisiloxane (DAPTMDS). The role of the disiloxane was to introduce terminal functional groups at the end of the polymer chains and to control the molecular weight of the polymers. Polymers with trimethyl, hydrido, vinyl, carboxypropyl and aminopropyl end-groups were obtained in this way. The structure of the ?,?-telechelic PDMSs was confirmed by NMR and IR spectroscopy. The molecular weights of the polymers were determined by 1H-NMR, gel permeation chromatography (GPC) and dilute solution viscometry. Thermogravimetric analysis (TGA) under nitrogen and air showed that the type of the terminal groups significantly influenced the thermal and thermo-oxidative stability, as well as the degradation mechanism of the ?,?-telechelic PDMSs.

scholarly journals Application of 1H DOSY NMR in Measurement of Polystyrene Molecular Weights

2020 ◽  
Vol 36 (2) ◽  
Author(s):  
Nguyen Hoai Nam ◽  
Nguyen Huu Tho ◽  
Nguyen Minh Ngoc ◽  
Pham Quang Trung
Keyword(s):  
Molecular Weight ◽  
Diffusion Coefficient ◽  
Hydrodynamic Radius ◽  
Gel Permeation Chromatography ◽  
Resonance Spectroscopy ◽  
Solvent Interaction ◽  
Molecular Weights ◽  
External Calibration Curve ◽  
Dosy Nmr

In this work, we studied the applicability of diffusion ordered nuclear magnetic resonance spectroscopy (DOSY NMR) as an alternative method in determination of polystyrene molecular weight. DOSY NMR spectroscopy allows measuring the diffusion coefficient of molecule which directly depend on hydrodynamic radius and so on, average molar mass in weight (Mw). By using commercial polystyrene (PS) standards, an external calibration curve was established. Based on the excellent linear correlation between diffusion coefficient (logD) and molecular weight (logM), the molecular weight of polystyrene can be predicted using the following equation . The validation was done by comparing with the Mw value obtained by gel permeation chromatography within less than 5% deviation. From the diffusion coefficient, some property of polystyrene in solution, such as Flory coefficient and polymer-solvent interaction, were also studied. The Flory coefficient confirmed that chloroform is a good solvent for PS.

scholarly journals Structural features of glycol-split low-molecular-weight heparins and their heparin lyase generated fragments

2013 ◽  
Vol 406 (1) ◽  
pp. 249-265 ◽  
Author(s):  
Anna Alekseeva ◽  
Benito Casu ◽  
Giuseppe Cassinelli ◽  
Marco Guerrini ◽  
Giangiacomo Torri ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Structural Features ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins
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