Exploitation of Glycoarrays -Translation to End-use

糖阵列的开发 - 转化为最终用途

• 批准号: EP/G037604/1
• 负责人: Sabine Flitsch
• 金额: $ 107.84万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG037604%2F1
• 关键词: Exploitation; Glycoarrays; Translation; End; use

Carbohydrates are a large group of compounds consisting of sugars with diverse structures present both inside and on the surface of cells. They fulfil many different roles but it is the way they interact with proteins that determines their effectiveness in a variety of biological events. Each cell contains a wide variety of carbohydrates and the number of possible combinations and interactions with proteins and with other carbohydrates is enormous. These interactions are known to have a major effect on tumour growth, infectious diseases, inflammation, neurodegeneration, wound healing and tissue engineering. For example, it is now known that one of the factors influencing whether or not the influenza virus invades humans or birds is due to a very small difference in the structure of one of the sugar molecules on the surface of epithelial cells in the lungs and respiratory tract. Cancer is associated with changes of the sugar molecules attached to some proteins on the cell surface; tracking such changes may therefore be useful for diagnosing cancer and to provide a solution for specifically targeting drugs at cancerous cells. These examples indicate the complexity of the field of glycomics and the need for rapid progress. During the past four years, a consortium of scientists from the UK has developed technology to measure the interactions between carbohydrates and proteins that happen in cells, tissues or organisms (a field called 'glycomics'). This technology is centered around arrays which contain the natural carbohydrates that one might find in a biological system. The arrays are created by printing tiny dots of the carbohydrates of interest onto a support such as a glass slide, exposing them to carbohydrate binding proteins (CBPs) and finally observing and analysing the interactions. The present proposal aims to apply this technology to important biological problems. For example, we will investigate the binding of carbohydrates to protein components of the human immune system, to viruses and bacteria and to enzymes that are linked to disease states such as congenital muscular dystrophy. We will also investigate possible routes of application and commercialisation of the technology in healthcare.

碳水化合物是由存在于细胞内部和表面的具有不同结构的糖组成的一大群化合物。它们发挥了许多不同的作用，但它们与蛋白质相互作用的方式决定了它们在各种生物事件中的有效性。每个细胞含有各种各样的碳水化合物，与蛋白质和其他碳水化合物的可能结合和相互作用的数量是巨大的。众所周知，这些相互作用对肿瘤生长、感染性疾病、炎症、神经退行性变、伤口愈合和组织工程具有重要影响。例如，现在已经知道，影响流感病毒是否入侵人类或鸟类的因素之一，是由于肺部和呼吸道上皮细胞表面的一种糖分子的结构存在很小的差异。癌症与附着在细胞表面某些蛋白质上的糖分子的变化有关；因此，跟踪这种变化可能有助于诊断癌症，并为专门针对癌细胞的药物提供解决方案。这些例子表明，糖组学领域十分复杂，需要迅速取得进展。在过去的四年里，来自英国的一个科学家联盟开发了一项技术，以测量细胞、组织或生物体中发生的碳水化合物和蛋白质之间的相互作用(这一领域被称为“糖组学”)。这项技术的中心是含有人们可能在生物系统中找到的天然碳水化合物的阵列。这些阵列是通过将感兴趣的碳水化合物的微小斑点打印到玻璃片等载体上，将它们暴露在碳水化合物结合蛋白(CBPS)中，最后观察和分析相互作用而形成的。本提案旨在将这项技术应用于重要的生物学问题。例如，我们将研究碳水化合物与人类免疫系统的蛋白质成分、病毒和细菌以及与先天性肌营养不良等疾病相关的酶的结合。我们还将调查这项技术在医疗保健领域应用和商业化的可能途径。

项目成果

Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity.

• DOI: 10.1039/c6mb00432f
• 发表时间: 2016-10-20
• 期刊: Molecular bioSystems
• 作者: Ahmed YA;Yates EA;Moss DJ;Loeven MA;Hussain SA;Hohenester E;Turnbull JE;Powell AK
• 通讯作者: Powell AK

Carbohydrate recognition in the immune system: contributions of neoglycolipid-based microarrays to carbohydrate ligand discovery.

• DOI: 10.1111/nyas.12210
• 发表时间: 2013-07
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Feizi T

Polysaccharide mimicry of the epitope of the broadly neutralizing anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycans

• DOI: 10.1093/glycob/cwq020
• 发表时间: 2010-07-01
• 期刊: GLYCOBIOLOGY
• 影响因子: 4.3
• 作者: Dunlop, D. Cameron;Bonomelli, Camille;Scanlan, Christopher N.
• 通讯作者: Scanlan, Christopher N.

Surface plasmon resonance imaging of glycoarrays identifies novel and unnatural carbohydrate-based ligands for potential ricin sensor development

• DOI: 10.1039/c1sc00120e
• 发表时间: 2011-01-01
• 期刊: CHEMICAL SCIENCE
• 影响因子: 8.4
• 作者: Fais, Margherita;Karamanska, Rositsa;Field, Robert A.
• 通讯作者: Field, Robert A.

Heparin increases the infectivity of Human Papillomavirus type 16 independent of cell surface proteoglycans and induces L1 epitope exposure.

肝素增加了独立于细胞表面蛋白聚糖的16型人乳头瘤病毒的感染性，并诱导L1表位暴露。

• DOI: 10.1111/cmi.12150
• 发表时间: 2013-11
• 期刊: Cellular microbiology
• 影响因子: 3.4
• 作者: Cerqueira C;Liu Y;Kühling L;Chai W;Hafezi W;van Kuppevelt TH;Kühn JE;Feizi T;Schelhaas M
• 通讯作者: Schelhaas M