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硫酸乙酰肝素及其衍生物和类似物具有可被利用的结构特征,特别是在抑制微生物附着方面。

Heparan sulphate, its derivatives and analogues share structural characteristics that can be exploited, particularly in inhibiting microbial attachment.

机构信息

Istituto di Chimica e Biochimica, Milano, Italy.

出版信息

Braz J Med Biol Res. 2012 May;45(5):386-91. doi: 10.1590/s0100-879x2012007500048. Epub 2012 Apr 5.

DOI:10.1590/s0100-879x2012007500048
PMID:22473323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3854285/
Abstract

Heparan sulphate (HS) and the related polysaccharide, heparin, exhibit conformational and charge arrangement properties, which provide a degree of redundancy allowing several seemingly distinct sequences to exhibit the same activity. This can also be mimicked by other sulphated polysaccharides, both in overall effect and in the details of interactions and structural consequences of interactions with proteins. Together, these provide a source of active compounds suitable for further development as potential drugs. These polysaccharides also possess considerable size, which bestows upon them an additional useful property: the capability of disrupting processes comprising many individual interactions, such as those characterising the attachment of microbial pathogens to host cells. The range of involvement of HS in microbial attachment is reviewed and examples, which include viral, bacterial and parasitic infections and which, in many cases, are now being investigated as potential targets for intervention, are identified.

摘要

硫酸乙酰肝素(HS)和相关多糖肝素具有构象和电荷排列特性,这为几种看似不同的序列提供了相同活性的冗余度。其他硫酸化多糖也可以模拟这种特性,无论是在整体效果还是在与蛋白质相互作用的细节以及相互作用的结构后果方面。这些为活性化合物提供了一个来源,这些化合物适合进一步开发为潜在药物。这些多糖还具有相当大的尺寸,这赋予了它们另一个有用的特性:能够破坏包含许多单个相互作用的过程,例如那些表征微生物病原体附着到宿主细胞的过程。综述了 HS 在微生物附着中的一系列作用,并确定了包括病毒、细菌和寄生虫感染在内的例子,在许多情况下,这些例子正在被作为潜在的干预靶点进行研究。

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本文引用的文献

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Productive dengue virus infection of human endothelial cells is directed by heparan sulfate-containing proteoglycan receptors.人内皮细胞中具有生产性的登革病毒感染是由含有肝素硫酸的蛋白聚糖受体所引导。
J Virol. 2011 Sep;85(18):9478-85. doi: 10.1128/JVI.05008-11. Epub 2011 Jul 6.
2
A systems biology approach for the investigation of the heparin/heparan sulfate interactome.系统生物学方法研究肝素/硫酸乙酰肝素相互作用组。
J Biol Chem. 2011 Jun 3;286(22):19892-904. doi: 10.1074/jbc.M111.228114. Epub 2011 Mar 30.
3
Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion.宿主细胞硫酸乙酰肝素蛋白聚糖在克氏锥虫无鞭毛体附着和入侵中的作用。
Parasitology. 2011 Apr;138(5):593-601. doi: 10.1017/S0031182010001678. Epub 2011 Jan 27.
4
Comparable stabilisation, structural changes and activities can be induced in FGF by a variety of HS and non-GAG analogues: implications for sequence-activity relationships.通过各种 HS 和非 GAG 类似物可以诱导 FGF 产生可比的稳定性、结构变化和活性:对序列-活性关系的影响。
Org Biomol Chem. 2010 Dec 7;8(23):5390-7. doi: 10.1039/c0ob00246a. Epub 2010 Sep 3.
5
Determining the anti-coagulant-independent anti-cancer effects of heparin.确定肝素不依赖抗凝作用的抗癌效果。
Br J Cancer. 2010 Aug 10;103(4):593-4. doi: 10.1038/sj.bjc.6605808. Epub 2010 Jul 20.
6
On the cytoadhesion of Plasmodium vivax-infected erythrocytes.关于感染疟原虫 vivax 的红细胞的细胞黏附。
J Infect Dis. 2010 Aug 15;202(4):638-47. doi: 10.1086/654815.
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Differential scanning fluorimetry measurement of protein stability changes upon binding to glycosaminoglycans: a screening test for binding specificity.用差示扫描荧光法测量蛋白质与糖胺聚糖结合时稳定性的变化:一种用于结合特异性筛选的测试方法。
Anal Chem. 2010 May 1;82(9):3796-802. doi: 10.1021/ac100188x.
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Proteoglycans in host-pathogen interactions: molecular mechanisms and therapeutic implications.宿主-病原体相互作用中的蛋白聚糖:分子机制及治疗意义。
Expert Rev Mol Med. 2010 Feb 1;12:e5. doi: 10.1017/S1462399409001367.
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Curr Pharm Des. 2009;15(25):2946-57. doi: 10.2174/138161209789058156.