Oversulfated chondroitin sulfate is not the sole contaminant in heparin

Pan, Jing; Qian, Yi; Zhou, Xiaodong; Pazandak, Andrew; Frazier, Sarah B.; Weiser, Peter; Lu, Hong; Zhang, Lijuan

doi:10.1038/nbt0310-203

Cited by 64 publications

(45 citation statements)

References 18 publications

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“…S2B). Consistent with our published observations that the heparins are not contaminated with OSCS alone (7,8); the published CE data (6,34) also showed that an OSHS co-migrated with heparin (see Ref. 6, supplemental Fig.…”

Section: Chemically Oversulfated Gags Were More Sulfated Thansupporting

confidence: 79%

“…2, A-D, lanes 12-15). The contaminated heparins had decreased levels of oversulfated GAG contamination in the order of OSCH4, OSLSCH5, S1, LSCH6, and G1 (8), which correlated with their ability in inducing kallikrein-and thrombin-like activities at the 200 g/ml level (Fig. 2, A-D, lanes 16 -20).…”

Section: Chemically Oversulfated Gags Were More Sulfated Thanmentioning

confidence: 88%

“…7, supplemental Table S1), we found that OSCS is not a major galactosamine containing heparin contaminants in any of the 34 samples when taking into account that the UV 200 nm absorbance response for OSCS is three times greater than that of heparin based on both CE-and galactosamine-based heparin contaminant quantifications (see Ref. 7, supplemental Table S1).…”

Section: Chemically Oversulfated Gags Were More Sulfated Thanmentioning

confidence: 95%

“…To this end, the human plasma was incubated with a series of negatively charged molecules at 37°C for 5 min. The compounds tested include different bacterial LPS, lipid A, yeast zymosan, DNA, phospholipids, sulfatide, chondroitin sulfate-A, chondroitin sulfate-E, porcine mucosa dermatan sulfate, heparan sulfate, and heparin by-products, over-sulfated forms of heparin by-products, heparan sulfate, chondroitin sulfate, dermatan sulfate, and five different types of contaminated heparin described previously (8), including heparin containing oversulfated contaminant (OSCH4), heparin containing both low sulfated and oversulfated contaminants (OSLSCH5), heparin containing OSHS (lot S1), heparin containing chemically sulfated/ desulfated GAGs (G1), heparin containing low sulfated heparin contaminant (LSCH6), and authentic heparin control purchased from Sigma. Kinetics of kallikrein-and thrombin-like activity induction was measured colorimetrically by kallikrein or thrombin substrate cleavage, respectively.…”

Section: Chemically Oversulfated Gags Were More Sulfated Thanmentioning

confidence: 99%

“…The less sulfated GAGs are removed from crude heparin into two heparin by-products named GAG waste and tank bottom (6). We have analyzed the same contaminated heparin preparations and concluded that heparin is contaminated either with chemically oversulfated/desulfated GAG waste or chemically oversulfated/desulfated GAG waste plus oversulfated tank bottom (7,8).…”

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confidence: 99%

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Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Pan

Qian

Zhou

et al. 2010

Journal of Biological Chemistry

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Contaminated heparin was associated with adverse reactions by activating the contact system. Chemically oversulfated/modified glycosaminoglycans (GAGs) consisting of heparan sulfate, dermatan sulfate, and chondroitin sulfate have been identified as heparin contaminants. Current studies demonstrated that each component of oversulfated GAGs was comparable with oversulfated chondroitin sulfate in activating the contact system. By testing a series of unrelated negatively charged compounds, we found that the contact system recognized negative charges rather than specific chemical structures. We further tested how oversulfated GAGs and contaminated heparins affect different cell signaling pathways. Our data showed that chemically oversulfated GAGs and contaminated heparin had higher activity than the parent compounds and authentic heparin, indicative of sulfation-dominant and GAG sequencedependent activities in BaF cell-based models of fibroblast growth factor/fibroblast growth factor receptor, glial cell linederived neurotrophic factor/c-Ret, and hepatocyte growth factor/c-Met signaling. In summary, these data indicate that contaminated heparins intended for blood anticoagulation not only activated the contact system but also modified different GAGdependent cell signaling pathways.

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Section: Chemically Oversulfated Gags Were More Sulfated Thansupporting

confidence: 79%

Section: Chemically Oversulfated Gags Were More Sulfated Thanmentioning

confidence: 88%

Section: Chemically Oversulfated Gags Were More Sulfated Thanmentioning

confidence: 95%

Section: Chemically Oversulfated Gags Were More Sulfated Thanmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Pan

Qian

Zhou

et al. 2010

Journal of Biological Chemistry

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Glycosaminoglycan Quality Control by Monosaccharide Analysis

Zhang

2021

Methods in Molecular Biology

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Structure and Physicochemical Characterisation of Heparin

Mulloy

2011

Heparin - A Century of Progress

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Heparin is a member of the heparan sulphate family of glycosaminoglycans, a linear polysaccharide with a complex sequence resulting from the action of post-polymerisation enzymes on a regular repeating disaccharide background. Its overall conformation is rod-like in solution as well as in the solid state, but the conformational fluctuations of iduronate residues give rise to considerable internal motion and variation in local three-dimensional structure. Structure/function relationships and their relation to sequence are still the subject of argument, but new methodologies to tackle the subject are emerging. Heparin as a therapeutic agent and as the object of research may be characterised by numerous physico-chemical techniques. These include chromatographic methods for measurement of molecular weight; a variety of spectroscopic techniques; separation methods for whole polysaccharides, as well as for oligo- and monosaccharides; and mass spectrometric methods for mapping and sequence analysis. The impetus provided by the discovery of heparin contamination with oversulphated chondroitin sulphate has been influential in bringing combinations of many old and new techniques into use to ensure that heparin is sufficiently consistent and pure to be used safely. Synthetic and semi-synthetic heparins are in development and may become reality in the relatively near future.

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Oversulfated chondroitin sulfate is not the sole contaminant in heparin

Cited by 64 publications

References 18 publications

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Chemically Oversulfated Glycosaminoglycans Are Potent Modulators of Contact System Activation and Different Cell Signaling Pathways

Glycosaminoglycan Quality Control by Monosaccharide Analysis

Structure and Physicochemical Characterisation of Heparin

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