heparitin sulfate


Summary: A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.

Top Publications

  1. Duchesne L, Octeau V, Bearon R, Beckett A, Prior I, Lounis B, et al. Transport of fibroblast growth factor 2 in the pericellular matrix is controlled by the spatial distribution of its binding sites in heparan sulfate. PLoS Biol. 2012;10:e1001361 pubmed publisher
    ..Similar mechanisms are likely to underpin the movement of many other HS-binding effectors. ..
  2. Holley R, Deligny A, Wei W, Watson H, Ninonuevo M, Dagälv A, et al. Mucopolysaccharidosis type I, unique structure of accumulated heparan sulfate and increased N-sulfotransferase activity in mice lacking ?-l-iduronidase. J Biol Chem. 2011;286:37515-24 pubmed publisher
    ..This mechanism may have severe implications during disease progression but, now identified, could help direct improved therapeutic strategies. ..
  3. Sapay N, Cabannes E, Petitou M, Imberty A. Molecular model of human heparanase with proposed binding mode of a heparan sulfate oligosaccharide and catalytic amino acids. Biopolymers. 2012;97:21-34 pubmed publisher
    ..The enzymatic mechanism investigated in the light of this new model allows for the proposal of several amino acids that can influence the protonation state of the nucleophile and the proton donor. ..
  4. Zhou H, Roy S, Cochran E, Zouaoui R, Chu C, Duffner J, et al. M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis. PLoS ONE. 2011;6:e21106 pubmed publisher
    ..These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis. ..
  5. Samsonov S, Teyra J, Pisabarro M. Docking glycosaminoglycans to proteins: analysis of solvent inclusion. J Comput Aided Mol Des. 2011;25:477-89 pubmed publisher
    ..Our work highlights the current challenges of introducing solvent in protein-GAGs recognition studies, which is crucial for exploiting the full potential of these molecules for rational engineering. ..
  6. Zaiss A, Lawrence R, Elashoff D, Esko J, Herschman H. Differential effects of murine and human factor X on adenovirus transduction via cell-surface heparan sulfate. J Biol Chem. 2011;286:24535-43 pubmed publisher
    ..These findings may have implications for murine models of adenovirus vector targeting. ..
  7. Maeda N, Ishii M, Nishimura K, Kamimura K. Functions of chondroitin sulfate and heparan sulfate in the developing brain. Neurochem Res. 2011;36:1228-40 pubmed publisher
    ..Recent studies have begun to reveal that the molecular interactions mediated by such glycosaminoglycan microdomains play critical roles in the various signaling pathways essential for the development of the brain. ..
  8. Bush K, Crawford B, Garner O, Nigam K, Esko J, Nigam S. N-sulfation of heparan sulfate regulates early branching events in the developing mammary gland. J Biol Chem. 2012;287:42064-70 pubmed publisher
    ..Together with previous work, the data indicate that different stages of ductal branching and lobuloalveolar formation are regulated by distinct sets of heparan sulfate biosynthetic enzymes in an appropriate growth factor context. ..
  9. Chang S, Mulloy B, Magee A, Couchman J. Two distinct sites in sonic Hedgehog combine for heparan sulfate interactions and cell signaling functions. J Biol Chem. 2011;286:44391-402 pubmed publisher
    ..These studies provide a new insight into the functional roles of hShh interactions with HSPGs, which may allow targeting this aspect of hShh biology in, for example, pancreatic ductal adenocarcinoma. ..

More Information


  1. Cain S, McGovern A, Baldwin A, Baldock C, Kielty C. Fibrillin-1 mutations causing Weill-Marchesani syndrome and acromicric and geleophysic dysplasias disrupt heparan sulfate interactions. PLoS ONE. 2012;7:e48634 pubmed publisher
    ..We show that a WMS deletion mutant, and five AD and GD point mutants all have disrupted heparin binding to TB5. These data provide insights into the biology of fibrillins and the pathologies of WMS, AD and GD. ..
  2. Sapay N, Cabannes E, Petitou M, Imberty A. Molecular modeling of the interaction between heparan sulfate and cellular growth factors: bringing pieces together. Glycobiology. 2011;21:1181-93 pubmed publisher
    ..This approach shed light on the plasticity of the growth factors interacting with heparan sulfate. This approach can be extended to the study of other protein/glycosaminoglycan complexes. ..
  3. Garner O, Bush K, Nigam K, Yamaguchi Y, Xu D, Esko J, et al. Stage-dependent regulation of mammary ductal branching by heparan sulfate and HGF-cMet signaling. Dev Biol. 2011;355:394-403 pubmed publisher
  4. Laguri C, Sapay N, Simorre J, Brutscher B, Imberty A, Gans P, et al. 13C-labeled heparan sulfate analogue as a tool to study protein/heparan sulfate interactions by NMR spectroscopy: application to the CXCL12? chemokine. J Am Chem Soc. 2011;133:9642-5 pubmed publisher
    ..This new approach provides a foundation for further investigations of protein/HS interactions and should find wide application. ..
  5. De Francesco M, Baronio M, Poiesi C. HIV-1 p17 matrix protein interacts with heparan sulfate side chain of CD44v3, syndecan-2, and syndecan-4 proteoglycans expressed on human activated CD4+ T cells affecting tumor necrosis factor alpha and interleukin 2 production. J Biol Chem. 2011;286:19541-8 pubmed publisher
    ..Moreover, we observed a stimulatory or inhibitory activity when CD4(+) T cells were activated with mitogens together with nanomolar or micromolar concentrations of the matrix protein. ..
  6. Huegel J, Sgariglia F, Enomoto Iwamoto M, Koyama E, Dormans J, Pacifici M. Heparan sulfate in skeletal development, growth, and pathology: the case of hereditary multiple exostoses. Dev Dyn. 2013;242:1021-32 pubmed publisher
    ..Insights from these studies suggest plausible and cogent ideas about how HME could be treated in the future. ..
  7. Anower E Khuda M, Matsumoto K, Habuchi H, Morita H, Yokochi T, Shimizu K, et al. Glycosaminoglycans in the blood of hereditary multiple exostoses patients: Half reduction of heparan sulfate to chondroitin sulfate ratio and the possible diagnostic application. Glycobiology. 2013;23:865-76 pubmed publisher
    ..The results suggest that HME patients' blood exhibited reduced HS amounts and HS/CS ratios, which could be used as a diagnostic biomarker for HME. ..
  8. Nasimuzzaman M, Persons D. Cell Membrane-associated heparan sulfate is a receptor for prototype foamy virus in human, monkey, and rodent cells. Mol Ther. 2012;20:1158-66 pubmed publisher
    ..Our findings indicate that cellular HS is a receptor for FV. Identifying FV receptor will enable better understanding of its entry process and optimal use as gene therapy vector to treat inherited and pathogenic diseases...
  9. Ali M, Karasneh G, Jarding M, Tiwari V, Shukla D. A 3-O-sulfated heparan sulfate binding peptide preferentially targets herpes simplex virus 2-infected cells. J Virol. 2012;86:6434-43 pubmed publisher
    ..In addition, our results also raise the possibility that 3-OS HS modifications within HS may be upregulated even more to accommodate for a significantly higher increase in the peptide binding to the infected cells. ..
  10. Sureau C, Salisse J. A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus a-determinant. Hepatology. 2013;57:985-94 pubmed publisher
    ..Our data provide new insight into the HBV entry pathway, including the opportunity to design antivirals directed to the AGL-HS interaction. ..
  11. Gardner C, Ebel G, Ryman K, Klimstra W. Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proc Natl Acad Sci U S A. 2011;108:16026-31 pubmed publisher
    ..Therefore, reinvestigation of HS binding by this and other arboviruses is warranted. ..
  12. Cecchi F, Pajalunga D, Fowler C, Uren A, Rabe D, Peruzzi B, et al. Targeted disruption of heparan sulfate interaction with hepatocyte and vascular endothelial growth factors blocks normal and oncogenic signaling. Cancer Cell. 2012;22:250-62 pubmed publisher
    ..Our findings illustrate the importance of HS in growth factor driven cancer progression and reveal an efficient strategy for therapeutic antagonist development. ..
  13. Nagamine S, Tamba M, Ishimine H, Araki K, Shiomi K, Okada T, et al. Organ-specific sulfation patterns of heparan sulfate generated by extracellular sulfatases Sulf1 and Sulf2 in mice. J Biol Chem. 2012;287:9579-90 pubmed publisher
    ..These findings indicate that Sulf1 and Sulf2 differentially contribute to the generation of organ-specific sulfation patterns of heparan sulfate. ..
  14. Holmborn K, Habicher J, Kasza Z, Eriksson A, Filipek Gorniok B, Gopal S, et al. On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis. J Biol Chem. 2012;287:33905-16 pubmed
  15. Kraushaar D, Rai S, Condac E, Nairn A, Zhang S, Yamaguchi Y, et al. Heparan sulfate facilitates FGF and BMP signaling to drive mesoderm differentiation of mouse embryonic stem cells. J Biol Chem. 2012;287:22691-700 pubmed publisher
    ..In summary, our study demonstrates that HS is required for ESC pluripotency, in particular lineage specification into mesoderm through facilitation of FGF and BMP signaling...
  16. Choudhary S, Marquez M, Alencastro F, Spors F, Zhao Y, Tiwari V. Herpes simplex virus type-1 (HSV-1) entry into human mesenchymal stem cells is heavily dependent on heparan sulfate. J Biomed Biotechnol. 2011;2011:264350 pubmed publisher
    ..Taken together, our results provide strong evidence demonstrating that HSV-1 is capable of infecting hMSCs and HS and 3-OS HS serve as its entry receptors during this process. ..
  17. Hirano K, van Kuppevelt T, Nishihara S. The transition of mouse pluripotent stem cells from the naïve to the primed state requires Fas signaling through 3-O sulfated heparan sulfate structures recognized by the HS4C3 antibody. Biochem Biophys Res Commun. 2013;430:1175-81 pubmed publisher
    ..This indicates that the HS4C3-binding epitope is necessary for the transition to the primed state. We propose that Fas signaling through the HS4C3-binding epitope contributes to the transition from the naïve state to the primed state. ..
  18. Noborn F, Ancsin J, Ubhayasekera W, Kisilevsky R, Li J. Heparan sulfate dissociates serum amyloid A (SAA) from acute-phase high-density lipoprotein, promoting SAA aggregation. J Biol Chem. 2012;287:25669-77 pubmed publisher
    ..The results address the initial events in the pathogenesis of AA amyloidosis. ..
  19. Nagai N, Habuchi H, Sugaya N, Nakamura M, Imamura T, Watanabe H, et al. Involvement of heparan sulfate 6-O-sulfation in the regulation of energy metabolism and the alteration of thyroid hormone levels in male mice. Glycobiology. 2013;23:980-92 pubmed publisher
  20. Irie F, Badie Mahdavi H, Yamaguchi Y. Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc Natl Acad Sci U S A. 2012;109:5052-6 pubmed publisher
    ..Our results demonstrate that heparan sulfate is critical for normal functioning of glutamatergic synapses and that its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism. ..
  21. Zaferani A, Vivès R, van der Pol P, Navis G, Daha M, van Kooten C, et al. Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate. J Biol Chem. 2012;287:31471-81 pubmed publisher
    ..These interactions can be manipulated with some low anticoagulant heparinoids, which can be important for preventing complement-derived tubular injury in proteinuric renal diseases. ..
  22. Costa T, dos Reis F, Lima A. Substrate inhibition and allosteric regulation by heparan sulfate of Trypanosoma brucei cathepsin L. Biochim Biophys Acta. 2012;1824:493-501 pubmed publisher
    ..We propose that brucipain shifts between an active and an inactive form as a result of temperature-dependent allosteric regulation. ..
  23. Ziolkowski A, Popp S, Freeman C, Parish C, Simeonovic C. Heparan sulfate and heparanase play key roles in mouse ? cell survival and autoimmune diabetes. J Clin Invest. 2012;122:132-41 pubmed publisher
    ..Our findings suggest that preservation of islet HS could be a therapeutic strategy for preventing T1D. ..
  24. Schwörer R, Zubkova O, Turnbull J, Tyler P. Synthesis of a targeted library of heparan sulfate hexa- to dodecasaccharides as inhibitors of ?-secretase: potential therapeutics for Alzheimer's disease. Chemistry. 2013;19:6817-23 pubmed publisher
  25. Haglund L, Tillgren V, Onnerfjord P, Heinegard D. The C-terminal peptide of chondroadherin modulates cellular activity by selectively binding to heparan sulfate chains. J Biol Chem. 2013;288:995-1008 pubmed publisher
  26. Ori A, Wilkinson M, Fernig D. A systems biology approach for the investigation of the heparin/heparan sulfate interactome. J Biol Chem. 2011;286:19892-904 pubmed publisher
    ..The evolutionary role of HS was reinforced by the presence of a rudimentary HS biosynthetic machinery in a unicellular organism at the root of the metazoan lineage. ..
  27. Ogata Iwao M, Inatani M, Iwao K, Takihara Y, Nakaishi Fukuchi Y, Irie F, et al. Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion cells. Invest Ophthalmol Vis Sci. 2011;52:6671-9 pubmed publisher
  28. Kraushaar D, Dalton S, Wang L. Heparan sulfate: a key regulator of embryonic stem cell fate. Biol Chem. 2013;394:741-51 pubmed publisher
    ..Finally, we discuss the applications of heparinoids and chemical inhibitors of HS biosynthesis for the manipulation of ESC culture and directed differentiation. ..
  29. Skidmore M, Guimond S, Dumax Vorzet A, Yates E, Turnbull J. Disaccharide compositional analysis of heparan sulfate and heparin polysaccharides using UV or high-sensitivity fluorescence (BODIPY) detection. Nat Protoc. 2010;5:1983-92 pubmed publisher
    ..Fluorescence detection can be routinely carried out in 3 d. ..
  30. Melrose J, Isaacs M, Smith S, Hughes C, Little C, Caterson B, et al. Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development. Histochem Cell Biol. 2012;138:461-75 pubmed publisher
  31. Wilkinson F, Holley R, Langford Smith K, Badrinath S, Liao A, Langford Smith A, et al. Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS ONE. 2012;7:e35787 pubmed publisher
    ..These data lend novel insight to MPS neuropathology, suggesting that MPSIIIA and IIIB have more pronounced neuropathology than MPSI, yet all are still progressive, at least in some aspects of neuropathology, from 4-9 months. ..
  32. Fadnes B, Uhlin Hansen L, Lindin I, Rekdal Ø. Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells. BMC Cancer. 2011;11:116 pubmed publisher
    ..In the present study, we have investigated the anticancer activity of three chemically modified 9-mer peptides and the influence of HS and chondroitin sulfate (CS) on their cytotoxic activity...
  33. Townley R, Bülow H. Genetic analysis of the heparan modification network in Caenorhabditis elegans. J Biol Chem. 2011;286:16824-31 pubmed publisher
    ..Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans. ..
  34. Jung J, Oh J, Kim Y, Shin M, Lee D, Chung J. Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin. J Korean Med Sci. 2012;27:300-6 pubmed publisher
    ..Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation. ..
  35. Wei W, Ninonuevo M, Sharma A, Danan Leon L, Leary J. A comprehensive compositional analysis of heparin/heparan sulfate-derived disaccharides from human serum. Anal Chem. 2011;83:3703-8 pubmed publisher
    ..Further applying this method, the comprehensive analysis of HSGAGs compositions in human sera from female donors showed considerable variations in disaccharide patterns and compositions. ..
  36. Dagälv A, Holmborn K, Kjellen L, Abrink M. Lowered expression of heparan sulfate/heparin biosynthesis enzyme N-deacetylase/n-sulfotransferase 1 results in increased sulfation of mast cell heparin. J Biol Chem. 2011;286:44433-40 pubmed publisher
    ..A model of the GAGosome, a hypothetical Golgi enzyme complex, is used to explain the results. ..
  37. Rai B, Nurcombe V, Cool S. Heparan sulfate-based treatments for regenerative medicine. Crit Rev Eukaryot Gene Expr. 2011;21:1-12 pubmed
  38. Christianson H, Svensson K, van Kuppevelt T, Li J, Belting M. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci U S A. 2013;110:17380-5 pubmed publisher
    ..We conclude that cancer cell-derived exosomes use HSPGs for their internalization and functional activity, which significantly extends the emerging role of HSPGs as key receptors of macromolecular cargo. ..
  39. Bambino Medeiros R, Oliveira F, Calvet C, Vicente D, Toma L, Krieger M, et al. Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion. Parasitology. 2011;138:593-601 pubmed publisher
    ..The knowledge of the mechanism triggered by heparan sulfate-binding T. cruzi proteins may provide new potential candidates for Chagas disease therapy. ..
  40. Tsuboi K, Hirakawa J, Seki E, Imai Y, Yamaguchi Y, Fukuda M, et al. Role of high endothelial venule-expressed heparan sulfate in chemokine presentation and lymphocyte homing. J Immunol. 2013;191:448-55 pubmed publisher
    ..These results suggest that chemokine presentation by HS on the surface of HEVs facilitates but is not absolutely required for lymphocyte homing. ..
  41. Tiwari V, Liu J, Valyi Nagy T, Shukla D. Anti-heparan sulfate peptides that block herpes simplex virus infection in vivo. J Biol Chem. 2011;286:25406-15 pubmed publisher
    ..This result also highlights an in vivo significance of HS and 3-OS HS during ocular herpes infection. ..
  42. Kleinschmit A, Takemura M, Dejima K, Choi P, Nakato H. Drosophila heparan sulfate 6-O-endosulfatase Sulf1 facilitates wingless (Wg) protein degradation. J Biol Chem. 2013;288:5081-9 pubmed publisher
    ..Our study demonstrates that vertebrate and Drosophila Sulfs have an intrinsically similar activity and that the function of Sulfs in the fate of Wnt/Wg ligands is context-dependent. ..
  43. Meade K, White K, Pickford C, Holley R, Marson A, Tillotson D, et al. Immobilization of heparan sulfate on electrospun meshes to support embryonic stem cell culture and differentiation. J Biol Chem. 2013;288:5530-8 pubmed publisher
    ..The combination of GAGs with electrospun scaffolds creates a biomaterial with potent applicability for the propagation and effective differentiation of pluripotent stem cells. ..
  44. Dalrymple N, Mackow E. Productive dengue virus infection of human endothelial cells is directed by heparan sulfate-containing proteoglycan receptors. J Virol. 2011;85:9478-85 pubmed publisher
  45. Huang Y, Shi X, Yu X, Leymarie N, Staples G, Yin H, et al. Improved liquid chromatography-MS/MS of heparan sulfate oligosaccharides via chip-based pulsed makeup flow. Anal Chem. 2011;83:8222-9 pubmed publisher
    ..Tandem MS of these supercharged precursor ions showed decreased abundances of product ions from sulfate losses yet more abundant product ions from backbone cleavages. ..
  46. Mosier P, Krishnasamy C, Kellogg G, Desai U. On the specificity of heparin/heparan sulfate binding to proteins. Anion-binding sites on antithrombin and thrombin are fundamentally different. PLoS ONE. 2012;7:e48632 pubmed publisher
    ..This provides a foundation for understanding specificity of interaction at an atomic level, which will greatly aid the design of natural or synthetic H/HS sequences that target proteins in a specific manner. ..
  47. Zielińska M, Sawosz E, Grodzik M, Wierzbicki M, Gromadka M, Hotowy A, et al. Effect of heparan sulfate and gold nanoparticles on muscle development during embryogenesis. Int J Nanomedicine. 2011;6:3163-72 pubmed publisher
    ..The results indicate that the administration of HS and nano-Au affects muscle development and that this effect is enhanced by conjugating HS with nano-Au. ..
  48. Attreed M, Desbois M, van Kuppevelt T, Bülow H. Direct visualization of specifically modified extracellular glycans in living animals. Nat Methods. 2012;9:477-9 pubmed publisher
    ..This experimental approach reveals a dynamic and cell-specific heparan sulfate landscape and could in principle be adapted to visualize and analyze any extracellular molecule in vivo. ..
  49. Kusche Gullberg M, Nybakken K, Perrimon N, Lindahl U. Drosophila heparan sulfate, a novel design. J Biol Chem. 2012;287:21950-6 pubmed publisher
    ..The N-sulfated domain may be envisaged as a heparin structure of unusually low O-sulfate content. ..
  50. Axelsson J, Xu D, Kang B, Nussbacher J, Handel T, Ley K, et al. Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice. Blood. 2012;120:1742-51 pubmed publisher
    ..This gain-of-function phenotype provides formidable evidence demonstrating the importance of endothelial heparan sulfate in inflammation and suggests a novel enzyme target for enhancing the innate immune response. ..
  51. Pempe E, Burch T, Law C, Liu J. Substrate specificity of 6-O-endosulfatase (Sulf-2) and its implications in synthesizing anticoagulant heparan sulfate. Glycobiology. 2012;22:1353-62 pubmed publisher
    ..Further understanding of Sulf-2 activity will help elucidate HS structure-function relationships and provide a valuable tool in tailoring HS-based anticoagulant drugs. ..
  52. Tiwari V, Maus E, Sigar I, Ramsey K, Shukla D. Role of heparan sulfate in sexually transmitted infections. Glycobiology. 2012;22:1402-12 pubmed publisher
    ..This review article summarizes the significance of HS in STIs and describes how emerging new products that target HS can be used to control the spread of STIs. ..