ＳＵＭＯ：ＳＢＭのタンパク質　－　タンパク質相互作用阻害剤の発見

SUMO：SBM 蛋白质 - 蛋白质相互作用抑制剂的发现

• 批准号: 12F02509
• 负责人: VOET ARNOUT (2013)
• 金额: $ 1.09万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12F02509/
• 关键词: SUMO-SIM; Inhibitor; In Silico; ALPHAscreen; NMR; EleKit; SUMO-SBM; バーチャルスクリーニング; Poisson-Boltzmann

Since the start of this project we have developed a computational approach to efficiently target protein-protein interactions, currently a hot topic in drug discovery. The sumo-sim interaction is essential in sumoylation and remains poorly understood. Therefore there is a need for a chemical probe to investigate this interaction. We have demonstrated the feasibility to target the SUMO-SIM interaction with druglike compounds for PPI inhibition as well as stimulation. These results have been published into 2 different publications. Given these promising results and after the development of the assays, a medium throughput screening experiment was set up and novel classes of compounds were identified that have possibly a more promising future for clinical usage. While this project is now terminated, it has opened a path to future research efforts as these compounds are interesting for optimization to analyse the sumo-SIM interactions and evaluate clinical usage (chemo and radio sensitization of cancer cells).Furthermore parallel with this research a novel method to utilize electrostatics for drug discovery targeting protein-protein interactions was developed and evaluated. This new method was also employed during the SAMPL4 virtual screening challenge and helped in obtained the highest ranking score.

自从这个项目开始以来，我们已经开发了一种计算方法来有效地针对蛋白质-蛋白质相互作用，这是目前药物发现中的一个热门话题。相扑-SIM相互作用在相扑过程中是必不可少的，目前仍知之甚少。因此，需要一种化学探针来研究这种相互作用。我们已经证明了以SUMO-SIM与类药物化合物的相互作用为靶点抑制和刺激PPI的可行性。这些结果已经发表在两个不同的出版物上。考虑到这些有希望的结果，在这些分析方法的发展之后，建立了一个中等吞吐量的筛选实验，并确定了可能具有更有希望的临床应用前景的新型化合物。虽然该项目现已终止，但它为未来的研究工作开辟了一条道路，因为这些化合物对于优化分析SUMO-SIM相互作用和评估临床应用(癌细胞的化学和放射增敏)是有意义的。此外，与此研究平行的是，我们开发并评估了一种利用静电学进行药物发现的新方法，该方法针对蛋白质-蛋白质相互作用。这一新方法也在SAMPL4虚拟筛选挑战中使用，并帮助获得了最高排名分数。

项目成果

Computational Methods for the discovery of SMPPII

发现 SMPPII 的计算方法

• 发表时间: 2013
• 作者: Tomonobu Nakayama. Jianxun Xu;Rhiannon Creasey;Yoshitama Shingaya and Masakazu Aono;Arnout R. D Voet
• 通讯作者: Arnout R. D Voet

Computational methods for the inhibition of SMPPII

SMPPII 抑制的计算方法

• 发表时间: 2013
• 作者: Voet A;Berenger F;Zhang KY.;Arnout Voet
• 通讯作者: Arnout Voet

Combining in silico and in cerebro approaches for virtual screening and pose prediction in SAMPL4

结合计算机和脑中方法在 SAMPL4 中进行虚拟筛选和姿势预测

• 发表时间: 2014
• 期刊: Journal Computer Aided Molecular Design
• 作者: Voet AR;Kumar A;Berenger F;Zhang KY.
• 通讯作者: Zhang KY.

Assay methods for small ubiquitin-like modifier (SUMO)-SUMO-interacting motif (SIM) interactions in vivo and in vitro using a split-luciferase complementation system

• DOI: 10.1016/j.ab.2013.12.009
• 发表时间: 2014-03-01
• 期刊: ANALYTICAL BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Hirohama, Mikako;Voet, Arnout R. D.;Yoshida, Minoru
• 通讯作者: Yoshida, Minoru