Retroviral integration into topologically-interlocked DNAs to probe the role of DNA structure and screen viral inhibitors

逆转录病毒整合到拓扑连锁的 DNA 中，以探测 DNA 结构的作用并筛选病毒抑制剂

• 批准号: 21K05274
• 负责人: A. RAJENDRAN
• 金额: $ 2.66万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K05274/
• 关键词: Topological structures; DNA nanotechnology; Minicircle DNA; DNA-protein interactions; Atomic force microscopy; DNA origami; Interlocked structures; DNA minicircles; HS-AFM; Viral inhibitor; Viral integrase; Drug screening

Topology-specific DNA structures, such as small loops, supercoils, knots, and catenated mini and maxicircles, occur in numerous instances in vivo. Besides their presence in vivo, synthetic molecules with interlocked units were achieved in macromolecular chemistry decades ago and are the current topic of interest in structural DNA nanotechnology. Due to the circular nature of these minicircles and interlocked DNAs, their structure and topology resemble nucleosomal DNA. Therefore, DNA minicircles with and without interlocked structures are attractive targets to probe the topological features of DNA and DNA-protein interactions. In this study, we aimed to design and prepare the DNA minicircles in free and topologically interlocked forms. These minicircles mimic nucleosomal DNA in terms of size and structure. Also, we have designed a frame-shaped DNA origami nanostructure and incorporated the topologically interlocked rotaxanes and catenanes. During our study, we noticed that these minicircles/interlocked structures and also the DNA origami frame are relatively unstable under application-specific conditions. Thus, before the investigation of the DNA-protein interactions and drug screening, it was necessary to stabilize these structures. We spent a reasonable amount of time in developing the stabilization methods for these DNA structures, and finally achieved stable substrates for the DNA-protein interactions and drug screening.

拓扑特异性DNA结构，如小环、超螺旋、结和链状小环和大环，在体内的许多情况下发生。除了它们在体内的存在，具有互锁单元的合成分子在几十年前在大分子化学中实现，并且是结构DNA纳米技术中当前感兴趣的主题。由于这些微环和互锁DNA的环状性质，它们的结构和拓扑结构类似于核小体DNA。因此，具有和不具有互锁结构的DNA微环是探测DNA和DNA-蛋白质相互作用的拓扑特征的有吸引力的靶标。在这项研究中，我们的目的是设计和制备自由和拓扑连锁形式的DNA微环。这些微环在大小和结构上模仿核小体DNA。此外，我们设计了一个框架状的DNA折纸纳米结构，并纳入拓扑联锁轮烷和索烃。在我们的研究中，我们注意到这些微环/互锁结构以及DNA折纸框架在特定应用条件下相对不稳定。因此，在研究DNA-蛋白质相互作用和药物筛选之前，有必要稳定这些结构。我们花了相当长的时间来开发这些DNA结构的稳定化方法，并最终获得了用于DNA-蛋白质相互作用和药物筛选的稳定底物。

项目成果

Tuning the reactivity of a substrate for SNAP-tag expands its application for recognition-driven DNA-protein conjugation

调整 SNAP 标签底物的反应性扩展了其在识别驱动的 DNA-蛋白质缀合方面的应用

• DOI: 10.1002/chem.202103304
• 发表时间: 2021
• 期刊: Chemistry-A European Journal
• 影响因子: 4.3
• 作者: Zhengxiao Zhang;Eiji Nakata;Huyen Dinh;Masayuki Saimura;Arivazhagan Rajendran;Kazunari Matsuda;Takashi Morii
• 通讯作者: Takashi Morii

Efficient ligation of nicks in DNA origami

DNA 折纸中切口的高效连接

• 发表时间: 2022
• 作者: A. Rajendran;K. Krishnamurthy;E. Nakata;T. Morii
• 通讯作者: T. Morii

Topologically-Interlocked Minicircles as Probes of DNA Topology and DNA-Protein Interactions

拓扑互锁小环作为 DNA 拓扑和 DNA-蛋白质相互作用的探针

• DOI: 10.1002/chem.202200108
• 发表时间: 2022
• 期刊: Chemistry-A European Journal
• 影响因子: 4.3
• 作者: Arivazhagan Rajendran;Kirankumar Krishnamurthy;Seojeong Park;Eiji Nakata;Youngjoo Kwon;Takashi Morii
• 通讯作者: Takashi Morii

Probing DNA Topology and DNA-Protein Interactions by Using Topologically-Interlocked DNA Structures

利用拓扑互锁的 DNA 结构探测 DNA 拓扑和 DNA-蛋白质相互作用

• 发表时间: 2021
• 作者: A. Rajendran;S. Park;E. Nakata;Y. Kwon;T. Morii
• 通讯作者: T. Morii

Implantable Microfluidic Device: An Epoch of Technology

植入式微流体装置：技术时代

• DOI: 10.2174/1381612827666210825114403
• 发表时间: 2022
• 期刊: Current Pharmaceutical Design
• 影响因子: 3.1
• 作者: A. Joseph;A. Rajendran;A. Karithikeyan;B.G. Nair
• 通讯作者: B.G. Nair