Heparan Sulfate
(Synonyms: 硫酸乙酰肝素) 目录号 : GC30767
硫酸乙酰肝素 (HS) 是一种复杂的聚阴离子多糖，广泛表达于细胞表面和细胞外基质。
Cas No.:9050-30-0
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Calu3 (lung epithelium) and Caco2 (intestinal epithelium) cells |
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Preparation Method |
Calu3 (lung epithelium) and Caco2 (intestinal epithelium) cells were infected with early passage SARS-CoV-2 pretreated with Heparan sulfate, and samples were collected 24 hours after infection. |
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Reaction Conditions |
0-500ug/ml Heparan sulfate,24h |
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Applications |
Heparan sulfate treatment significantly reduced SARS-CoV-2 replication in cell lysates and supernatant samples of Calu3 and Caco2. |
| Animal experiment [2]: | |
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Animal models |
Sprague-Dawley male rats 3-4 months old |
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Preparation Method |
Groups of rats (n = 5) received a piece of Gelfoam embedded with human recombinant FGF-2 dissolved in PBS, Heparan sulfate (HS; 10 μg/ml) dissolved in PBS, or both, in the right hemispheres. |
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Dosage form |
A piece of Gelfoam embedded with 10 ug/ml Heparan sulfate for two days |
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Applications |
FGF-2/FGFR system is involved in the regulation of astrocytic reactivity and/or proliferation in the brain and its action is potentiated by Heparan sulfate. |
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References: [1]. Chu H, Hu B, et,al. Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun. 2021 Jan 8;12(1):134. doi: 10.1038/s41467-020-20457-w. PMID: 33420022; PMCID: PMC7794309. [2]. Gómez-Pinilla F, Vu L, et,al. Regulation of astrocyte proliferation by FGF-2 and heparan sulfate in vivo. J Neurosci. 1995 Mar;15(3 Pt 1):2021-9. doi: 10.1523/JNEUROSCI.15-03-02021.1995. PMID: 7891149; PMCID: PMC6578134. |
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Heparan sulfate (HS) is a complex, polyanionic polysaccharide ubiquitously expressed on cell surfaces and in the extracellular matrix[1]. Heparan sulfate interacts with numerous proteins, including growth factors, morphogens, and adhesion molecules, and thereby regulates important developmental processes in invertebrates and vertebrates[6]. Heparan sulfate proteoglycans can act as receptors for proteases and protease inhibitors regulating their spatial distribution and activity. Membrane Heparan sulfate proteoglycans act as coreceptors for various tyrosine kinase-type growth factor receptors, lowering their activation threshold or changing the duration of signaling reactions[5].
Heparan sulfate treatment significantly reduced SARS-CoV-2 replication in cell lysates and supernatant samples of Calu3 and Caco2. HS serves as an essential host determinant during SARS-CoV-2 attachment and replication[2].Heparan sulfate influences the binding affinity of intestinal epithelium cells to Wnt, thereby promoting activation of canonical Wnt signaling and facilitating regeneration of small intestinal crypts after epithelial injury[7].
In Sprague-Dawley male rats, FGF-2/FGFR system is involved in the regulation of astrocytic reactivity and/or proliferation in the brain and its action is potentiated by Heparan sulfate [3].Heparan sulfate proteoglycans represent a major component of the extracellular matrix and are critical for brain development, Heparan Sulfate can maintain neuronal excitability, promote synaptic plasticity and learning[5].
References:
[1]: Chhabra M, Doherty GG, et,al. From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions. Chem Rec. 2021 Nov;21(11):3087-3101. doi: 10.1002/tcr.202100125. Epub 2021 Jun 19. PMID: 34145723; PMCID: PMC8441866.
[2]: Chu H, Hu B, et,al. Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat Commun. 2021 Jan 8;12(1):134. doi: 10.1038/s41467-020-20457-w. PMID: 33420022; PMCID: PMC7794309.
[3]: Gómez-Pinilla F, Vu L, et,al. Regulation of astrocyte proliferation by FGF-2 and heparan sulfate in vivo. J Neurosci. 1995 Mar;15(3 Pt 1):2021-9. doi: 10.1523/JNEUROSCI.15-03-02021.1995. PMID: 7891149; PMCID: PMC6578134.
[4]: Minge D, Senkov O, et,al. Heparan Sulfates Support Pyramidal Cell Excitability, Synaptic Plasticity, and Context Discrimination. Cereb Cortex. 2017 Feb 1;27(2):903-918. doi: 10.1093/cercor/bhx003. PMID: 28119345; PMCID: PMC5390399.
[5]: Sarrazin S, Lamanna WC, et,al. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011 Jul 1;3(7):a004952. doi: 10.1101/cshperspect.a004952. PMID: 21690215; PMCID: PMC3119907.
[6]: Kraushaar DC, Dalton S, et,al. Heparan sulfate: a key regulator of embryonic stem cell fate. Biol Chem. 2013 Jun;394(6):741-51. doi: 10.1515/hsz-2012-0353. PMID: 23370908; PMCID: PMC3933957.
[7]: Yamamoto S, Nakase H, et,al. Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling. Am J Physiol Gastrointest Liver Physiol. 2013 Aug 1;305(3):G241-9. doi: 10.1152/ajpgi.00480.2012. Epub 2013 Jun 6. PMID: 23744737; PMCID: PMC3742857.
硫酸乙酰肝素 (HS) 是一种复杂的聚阴离子多糖,广泛表达于细胞表面和细胞外基质[1]。硫酸乙酰肝素与许多蛋白质相互作用,包括生长因子、形态发生素和粘附分子,从而调节无脊椎动物和脊椎动物的重要发育过程[6]。硫酸乙酰肝素蛋白聚糖可以作为蛋白酶和蛋白酶抑制剂的受体,调节它们的空间分布和活性。膜硫酸乙酰肝素蛋白多糖作为多种酪氨酸激酶型生长因子受体的辅助受体,降低其激活阈值或改变信号反应的持续时间[5]。
硫酸乙酰肝素处理显着降低了 Calu3 和 Caco2 细胞裂解物和上清液样品中的 SARS-CoV-2 复制。 HS 在 SARS-CoV-2 附着和复制过程中作为重要的宿主决定因素[2]。硫酸乙酰肝素影响肠上皮细胞与 Wnt 的结合亲和力,从而促进经典 Wnt 信号通路的激活并促进再生上皮损伤后小肠隐窝的形成[7].
在 Sprague-Dawley 雄性大鼠中,FGF-2/FGFR 系统参与脑内星形胶质细胞反应性和/或增殖的调节,硫酸乙酰肝素可增强其作用[3]。硫酸乙酰肝素蛋白多糖是细胞外基质的主要成分,对大脑发育至关重要,硫酸乙酰肝素可维持神经元兴奋性,促进突触可塑性和学习[5]。
| Cas No. | 9050-30-0 | SDF | |
| 别名 | 硫酸乙酰肝素 | ||
| Canonical SMILES | O=S(OCC1O[C@@H](OC)[C@@H](NS(=O)([O-])=O)[C@@H](OS(=O)([O-])=O)[C@H]1O[C@@H]2OC(C([O-])=O)[C@H](O[C@@H]3OC(COS(=O)([O-])=O)[C@H](O[C@@H]4OC(C([O-])=O)[C@H](OC)[C@H](O)[C@@H]4OS(=O)([O-])=O)[C@H](O)[C@@H]3NS(=O)([O-])=O)[C@H](O)[C@@H]2O)([O-])=O.[n] | ||
| 分子式 | C12H19NO20S3 (monomer) | 分子量 | 593.47(monomer) |
| 溶解度 | Water : 47.1 mg/mL | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.685 mL | 8.425 mL | 16.8501 mL |
| 5 mM | 0.337 mL | 1.685 mL | 3.37 mL |
| 10 mM | 0.1685 mL | 0.8425 mL | 1.685 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Heparan Sulfate: Biosynthesis, Structure, and Function
Heparan sulfate (HS) proteoglycans (PGs) are ubiquitously expressed on cell surfaces and in the extracellular matrix of most animal tissues, having essential functions in development and homeostasis, as well as playing various roles in disease processes. The functions of HSPGs are mainly dependent on interactions between the HS-side chains with a variety of proteins including cytokines, growth factors, and their receptors. In a given HS polysaccharide, negatively charged sulfate and carboxylate groups are arranged in various types of domains, generated through strictly regulated biosynthetic reactions and with enormous potential for structural variability. The mode of HS-protein interactions is assessed through binding experiments using saccharides of defined composition in vitro, signaling assays in cell models where HS structures are manipulated, and targeted disruption of genes for biosynthetic enzymes in animals (mouse, zebrafish, Drosophila, and Caenorhabditis elegans) followed by phenotype analysis. Whereas some protein ligands appear to require strictly defined HS structure, others bind to variable saccharide domains without apparent dependence on distinct saccharide sequence. These findings raise intriguing questions concerning the functional significance of regulation in HS biosynthesis and the potential for development of therapeutics targeting HS-protein interactions.
Heparan Sulfate in the Tumor Microenvironment
The biology of tumor cells strictly depends on their microenvironment architecture and composition, which controls the availability of growth factors and signaling molecules. Thus, the network of glycosaminoglycans, proteoglycans, and proteins known as extracellular matrix (ECM) that surrounds the cells plays a central role in the regulation of tumor fate. Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) are highly versatile ECM components that bind and regulate the activity of growth factors, cell membrane receptors, and other ECM molecules. These HS binding partners modulate cell adhesion, motility, and proliferation that are processes altered during tumor progression. Modification in the expression and activity of HS, HSPGs, and the respective metabolic enzymes results unavoidably in alteration of tumor cell microenvironment. In this light, the targeting of HS structure and metabolism is potentially a new tool in the treatment of different cancer types.
Is heparan sulfate a target for inhibition of RNA virus infection?
Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a cofactor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.
A Systems View of the Heparan Sulfate Interactome
Heparan sulfate proteoglycans consist of a small family of proteins decorated with one or more covalently attached heparan sulfate glycosaminoglycan chains. These chains have intricate structural patterns based on the position of sulfate groups and uronic acid epimers, which dictate their ability to engage a large repertoire of heparan sulfate-binding proteins, including extracellular matrix proteins, growth factors and morphogens, cytokines and chemokines, apolipoproteins and lipases, adhesion and growth factor receptors, and components of the complement and coagulation system. This review highlights recent progress in the characterization of the so-called "heparan sulfate interactome," with a major focus on systems-wide strategies as a tool for discovery and characterization of this subproteome. In addition, we compiled all heparan sulfate-binding proteins reported in the literature to date and grouped them into a few major functional classes by applying a networking approach.
PI-88 and Related Heparan Sulfate Mimetics
The heparan sulfate mimetic PI-88 (muparfostat) is a complex mixture of sulfated oligosaccharides that was identified in the late 1990s as a potent inhibitor of heparanase. In preclinical animal models it was shown to block angiogenesis, metastasis and tumor growth, and subsequently became the first heparanase inhibitor to enter clinical trials for cancer. It progressed to Phase III trials but ultimately was not approved for use. Herein we summarize the preparation, physicochemical and biological properties of PI-88, and discuss preclinical/clinical and structure-activity relationship studies. In addition, we discuss the PI-88-inspired development of related HS mimetic heparanase inhibitors with improved properties, ultimately leading to the discovery of PG545 (pixatimod) which is currently in clinical trials.