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Heparin Oligosaccharides (heparin + oligosaccharide)

Distribution by Scientific Domains

Chemistry	83%

Selected Abstracts

De Novo Synthesis of Uronic Acid Building Blocks for Assembly of Heparin Oligosaccharides

CHEMISTRY - A EUROPEAN JOURNAL, Issue 16 2007
Alexander Adibekian
Abstract An efficient de novo synthesis of uronic acid building blocks is described. The synthetic strategy relies on the stereoselective elongation of thioacetal protected dialdehydes 12,a and 17. The dialdehydes are prepared from D -xylose, a cheap and commercially available source. A highly stereoselective MgBr2,OEt2 -mediated Mukaiyama aldol addition to C4-aldehyde 12,a is performed to obtain D -glucuronic acid building block 16, whereas L -iduronic acid building block 22 is prepared by MgBr2,OEt2 -mediated cyanation of C5-aldehyde 17. Synthesis of a heparin disaccharide demonstrates the utility of the de novo strategy for the assembly of glycosaminoglycan oligosaccharides. [source]

Preparation and Use of Microarrays Containing Synthetic Heparin Oligosaccharides for the Rapid Analysis of Heparin,Protein Interactions

CHEMISTRY - A EUROPEAN JOURNAL, Issue 34 2006
Christian Noti
Abstract Heparin is a highly sulfated, linear polymer that participates in a plethora of biological processes by interaction with many proteins. The chemical complexity and heterogeneity of this polysaccharide can explain the fact that, despite its widespread medical use as an anticoagulant drug, the structure,function relationship of defined heparin sequences is still poorly understood. Here, we present the chemical synthesis of a library containing heparin oligosaccharides ranging from di- to hexamers of different sequences and sulfation patterns. An amine-terminated linker was placed at the reducing end of the synthetic structures to allow for immobilization onto N -hydroxysuccinimide activated glass slides and creation of heparin microarrays. Key features of this modular synthesis, such as the influence of the amine linker on the glycosidation efficiency, the use of 2-azidoglucose as glycosylating agents for oligosaccharide assembly, and the compatibility of the protecting group strategy with the sulfation-deprotection steps, are discussed. Heparin microarrays containing this oligosaccharide library were constructed using a robotic printer and employed to characterize the carbohydrate binding affinities of three heparin-binding growth factors. FGF-1, FGF-2 and FGF-4 that are implicated in angiogenesis, cell growth and differentiation were studied. These heparin chips aided in the discovery of novel, sulfated sequences that bind FGF, and in the determination of the structural requirements needed for recognition by using picomoles of protein on a single slide. The results presented here highlight the potential of combining oligosaccharide synthesis and carbohydrate microarray technology to establish a structure,activity relationship in biological processes. [source]

An interaction between opticin and heparan sulfate may provide the molecular basis for vitreoretinal adhesion

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004
V. John Hindson
Introduction Opticin is a member of the extracellular matrix small leucine-rich repeat (SLRP) proteoglycan/protein family, which was originally identified in the eye associated with the collagen fibrils of the vitreous humour. A putative heparin/heparan sulfate (HS) binding motif (RKERKRR) was identified at the N-terminus of human opticin, but this is absent in the bovine form. Furthermore, the strength of attachment between the vitreous and the retina was observed to be species-dependent and related to the presence or absence of this motif. We hypothesized that opticin cross-links the collagen fibrils of the vitreous to HS proteoglycans in the inner limiting lamina (a basement membrane on the inner surface of the retina), contributing towards vitreoretinal adhesion. Materials and methods Recombinant human and bovine opticin were expressed in 293-EBNA cells and purified to apparent homogeneity. Solid phase assays and surface plasmon resonance studies were used to characterize interactions between immobilized heparin/HS and opticin. Results Solid phase and BIAcore data revealed that human opticin binds heparin/HS and binds to heparin with a dissociation constant of approximately 20 nm. By contrast bovine opticin, which lacks the basic cluster, bound severalfold less tightly. Competition studies with heparin oligosaccharides indicated that the heparin/HS binding site is greater than 6 monosaccharides in length. Heparin, HS, chondroitin sulfate A (CS-A), dermatan sulfate and hyaluronan all competed with heparin for binding to human opticin but CS-C did not. Discussion Work to date suggests that the N-terminal sequence RKERKRR contributes significantly to the binding of opticin to heparin/HS. Vitreoretinal adhesion plays a key role in a number of eye diseases and inhibitors of the opticin,HS interaction could be of therapeutic value. [source]

Structural and interaction analysis of helical heparin oligosaccharides with the fragment molecular orbital method

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 9 2009
Toshihiko Sawada
Abstract The fragment molecular orbital method (FMO) was applied to the geometry optimization of several heparin oligosaccharides at the RHF/6-31(+)G(d) level combined with the polarizable continuum model (PCM). For comparison, GLYCAM force field optimization in explicit solvent was also conducted. Good accuracy of FMO was demonstrated in comparison to ab initio at the MP2/PCM level. The interaction analysis was conducted using the pair interaction energy decomposition analysis (PIEDA), and the role of hydrogen bonding and solvent was elucidated in the helix formation of heparin in solution. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source]