Probing Structural Selectivity of Synthetic Heparin Binding to Stabilin Protein Receptors

Pempe, Elizabeth H.; Xu, Yongmei; Gopalakrishnan, Sandhya; Liu, Jian; Harris, Edward N.

doi:10.1074/jbc.m111.320069

Cited by 40 publications

(59 citation statements)

References 41 publications

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“…We mixed 0.35 ml of the cell lysate mixture with 4 ml scintillation fluid (PerkinElmer) and measured radioactivity by a Beckman Coulter LS6500 scintillation counter. Receptor-specific internalization was assessed by incubating each radio labeled ligand with at least a 100-fold excess of unlabeled UFH 17 . The remaining 0.05 ml cell lysate was used to determine protein concentrations using the Bradford reagent (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…The conversion of GlcA to IdoA2S involves two steps: C 5 -epi catalyzes epimerization of a GlcA to an IdoA, and 2-O-sulfotransferase (2-OST) transfers a sulfate group to IdoA. C 5 -epi catalyzes both the forward and reverse reactions, leading to the incomplete conversion of GlcA to IdoA2S 16 and a complex mixture of products 17 . The placement of a pentasaccharide domain, GlcN-trifluoroacetyl(TFA)-GlcA-GlcNS-GlcA-GlcNS, into the substrate directs C 5 -epi to irreversibly react with only the GlcA residue flanked with two GlcNS residues and avoids incomplete conversion.…”

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confidence: 99%

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Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

et al. 2014

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Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

et al. 2014

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“…Clearance of circulating heparin occurs primarily in liver sinusoidal endothelial cells by stabilin-1 and −2 in a manner that appears to be enhanced by 3- O sulfation (Borjigin et al, 2003; Pempe et al, 2012). Stabilin-1 and −2 overexpressing cells took up Hs3st-1-modified oligosaccharide more efficiently than an identical non-3- O -sulfated oligosaccharide.…”

Section: Biochemical and Physiological Implications Of 3-o-sulfationmentioning

confidence: 99%

Heparan sulfate 3-O-sulfation: A rare modification in search of a function

Thacker¹,

Xu²,

Lawrence³

et al. 2014

Matrix Biology

199

244

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Many protein ligands bind to heparan sulfate, which results in their presentation, protection, oligomerization or conformational activation. Binding depends on the pattern of sulfation and arrangement of uronic acid epimers along the chains. Sulfation at the C3 position of glucosamine is a relatively rare, yet biologically significant modification, initially described as a key determinant for binding and activation of antithrombin and later for infection by Type I Herpes Simplex virus. In mammals, a family of seven heparan sulfate 3-O-sulfotransferases installs sulfate groups at this position and constitutes the largest group of sulfotransferases involved in heparan sulfate formation. However, to date very few proteins or biological systems have been described that are influenced by 3-O-sulfation. This review describes our current understanding of the prevalence and structure of 3-O-sulfation sites, expression and substrate specificity of the 3-O-sulfotransferase family and the emerging roles of 3-O-sulfation in biology.

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“…14,15 Evidence is also emerging about the importance of glucosamine 3-O-sulfation in development and cancer. 16 NMR spectroscopy is a well-established analytical tool for the structural characterization of heparin and heparan sulfate.…”

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¹H and ¹⁵N NMR Characterization of the Amine Groups of Heparan Sulfate Related Glucosamine Monosaccharides in Aqueous Solution

Beecher

Larive

2015

Anal. Chem.

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Glucosamine is an important constituent of the heterogeneous glycosaminoglycans heparin and heparan sulfate occurring in N-acetylated and N-sulfated forms, and as the unmodified amine. Though the (1)H and (15)N NMR chemical shifts of N-acetyl- and N-sulfoglucosamine residues have been extensively characterized, this study provides the first direct NMR characterization of the amine groups of glucosamine and 3-O-sulfoglucosamine in aqueous solution. The solvent exchange properties of the amine protons are examined, and the possibility of a salt bridge between the sulfate and amine groups of 3-O-sulfoglucosamine is explored through (1)H NMR pKa measurements but is not supported by the experimental results.

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Probing Structural Selectivity of Synthetic Heparin Binding to Stabilin Protein Receptors

Cited by 40 publications

References 41 publications

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Heparan sulfate 3-O-sulfation: A rare modification in search of a function

¹H and ¹⁵N NMR Characterization of the Amine Groups of Heparan Sulfate Related Glucosamine Monosaccharides in Aqueous Solution

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Probing Structural Selectivity of Synthetic Heparin Binding to Stabilin Protein Receptors

Cited by 40 publications

References 41 publications

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Heparan sulfate 3-O-sulfation: A rare modification in search of a function

1H and 15N NMR Characterization of the Amine Groups of Heparan Sulfate Related Glucosamine Monosaccharides in Aqueous Solution

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¹H and ¹⁵N NMR Characterization of the Amine Groups of Heparan Sulfate Related Glucosamine Monosaccharides in Aqueous Solution