Developing and investigating an ultra-stable molecular hub for bionanotechnology

开发和研究生物纳米技术的超稳定分子中心

• 批准号: BB/I006303/1
• 负责人: Mark Howarth
• 金额: $ 43.24万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI006303%2F1
• 关键词: Developing; investigating; ultra; stable; molecular

When biologists wish to isolate or immobilise an object (proteins, DNA, RNA, sugars, small organic molecules, nanoparticles), they will very often attach the vitamin biotin to this object, so that the object can be captured by the protein streptavidin. The link from biotin to streptavidin is one of the strongest known in nature, but this link can be broken in challenging situations, so limiting many biological experiments and devices. We have made an altered streptavidin which forms an even stronger link to biotin, so that biotin is captured for longer and stays bound in harsher conditions. We plan to determine at the atomic level why this new interaction is stronger. This insight should help to illuminate the basis of ultra-strong binding, and so assist the design of drugs that can bind more stably to their targets and thus be more effective. We will also engineer streptavidin so that it can anchor two different kinds of molecules, enabling biologists to create new assemblies to combine and control the functions of biomolecules. We ourselves will use these assemblies to explore how growth factors can either work together or compete in transmitting signals inside the cell, so determining whether the cell lives, dies, or divides.

当生物学家希望分离或固定物体（蛋白质，DNA，RNA，糖，小有机分子，纳米颗粒）时，它们通常会将维生素生物素连接到该物体上，以便该物体可以被蛋白链霉素捕获。从生物素到链霉亲和素的联系是自然界中最强的联系之一，但是在具有挑战性的情况下，这种链接可能会破裂，因此限制了许多生物学实验和设备。我们做出了一种改变的链霉亲和素，与生物素形成更强的联系，以便将生物素捕获更长的时间并保持在更恶劣的条件下。我们计划在原子水平上确定为什么这种新相互作用更强。这种洞察力应有助于阐明超强结合的基础，从而帮助设计可以更稳定地与目标结合并因此更有效的药物设计。我们还将设计链霉亲和素，以便它可以锚定两种不同的分子，从而使生物学家能够创建新的组件来结合和控制生物分子的功能。我们自己将使用这些组件来探索生长因素如何共同工作或竞争在细胞内传输信号，从而确定细胞的生命，死亡还是分裂。

项目成果

SpyAvidin hubs enable precise and ultrastable orthogonal nanoassembly.

• DOI: 10.1021/ja505584f
• 发表时间: 2014-09-03
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Fairhead, Michael;Veggiani, Gianluca;Lever, Melissa;Yan, Jun;Mesner, Dejan;Robinson, Carol V.;Dushek, Omer;van der Merwe, P. Anton;Howarth, Mark
• 通讯作者: Howarth, Mark

Site-specific biotinylation of purified proteins using BirA.

• DOI: 10.1007/978-1-4939-2272-7_12
• 发表时间: 2015
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Fairhead, Michael;Howarth, Mark
• 通讯作者: Howarth, Mark

Optimized Streptavidin for Fluorescent Labeling of Biotinylated Targets

用于生物素化靶标荧光标记的优化链霉亲和素

• DOI: 10.1016/j.chembiol.2017.07.013
• 发表时间: 2017
• 期刊: Cell Chemical Biology
• 影响因子: 8.6
• 作者: Hytönen V

Simultaneous identification of viruses and viral variants with programmable DNA nanobait.

• DOI: 10.1038/s41565-022-01287-x
• 发表时间: 2023-03
• 期刊: Nature nanotechnology
• 影响因子: 38.3

Plug-and-play pairing via defined divalent streptavidins.

• DOI: 10.1016/j.jmb.2013.09.016
• 发表时间: 2014-01-09
• 期刊: JOURNAL OF MOLECULAR BIOLOGY
• 影响因子: 5.6
• 作者: Fairhead, Michael;Krndija, Denis;Lowe, Ed D.;Howarth, Mark
• 通讯作者: Howarth, Mark