ＳＵＭＯ：ＳＢＭのタンパク質　－　タンパク質相互作用阻害剤の発見

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靶向蛋白质-蛋白质相互作用，这是目前药物发现的热门话题。sumo-sim相互作用在sumo化中是必不可少的，但人们对其了解甚少。因此，需要一种化学探针来研究这种相互作用。我们已经证明了将SUMO-SIM与药物样化合物相互作用作为PPI抑制和刺激的可行性。这些结果发表在两份不同的出版物上。考虑到这些有希望的结果，在分析开发之后，建立了中等通量筛选实验，并确定了可能具有更有前景的临床应用的新型化合物。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，因为这些化合物对优化分析sumo-SIM相互作用和评估临床应用（癌细胞的化疗和放射增敏）很有趣。此外，与本研究平行的是一种利用静电发现靶向蛋白质-蛋白质相互作用药物的新方法。在SAMPL4虚拟筛选挑战中也采用了这种新方法，并获得了最高的排名分数。

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.