特殊ペプチド・フォールダマーハイブリッド分子の研究

特殊肽折叠分子杂化分子的研究

• 批准号: 22KF0096
• 负责人: 菅 裕明
• 金额: $ 1.47万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2023
• 资助国家: 日本
• 起止时间: 2023-03-08 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22KF0096/
• 关键词: Bioorthogonal chemistry; Cross-coupling chemistry

I have been working towards developing a new bioorthogonal intramolecular amide alkylation method for the past year. The goal is to have a reactive amino acid side chain moiety that, upon activation with light or reactants/catalysts, can cyclize onto the neighboring amide nitrogen. Reaction conditions must be bioorthogonal and compatible to be used in in vitro peptide translation and the mRNA display screening platform RaPID. However, despite our extensive efforts, none of the proposed methods have proven successful so far.Several different approaches were investigated, including photochemical activation of diazirine and fluorenol containing compounds. Furthermore, metal-catalyzed cross-couplings, particularly utilizing Pd0 as well as CuI and CuII containing catalysts, in aqueous conditions were tested. Unfortunately, despite the initial promise and many iterations of these reaction methods, we have not achieved the desired outcome of a bioorthogonal amide alkylation.Despite these setbacks, I remain hopeful that continued exploration of new reaction mechanisms and synthetic strategies will eventually lead to success in this area. Furthermore, I believe that the knowledge gained from these failed attempts will prove valuable in the development of future chemical biology techniques and applications. Overall, while the search for a new bioorthogonal amide alkylation method has been challenging, I remain committed to advancing the field and developing innovative solutions to this problem.

在过去的一年中，我一直在努力开发一种新的生物色粒分子内酰胺烷基化方法。目的是具有一个反应性氨基酸侧链部分，该部分用光或反应物/催化剂激活后，可以在相邻的酰胺氮上循环。反应条件必须是生物方向的，并且可以兼容才能在体外肽翻译和mRNA显示筛选平台快速中使用。然而，尽管我们进行了广泛的努力，但迄今为止，未经证明的方法都没有被证明是成功的。研究了不同的方法，包括重氮嗪和含有化合物的氟烯醇的光化学激活。此外，测试了在水性条件下的金属催化的交叉耦合，特别是利用PD0以及含有CUI和CUII的CUII。不幸的是，尽管这些反应方法有最初的希望和许多迭代，但我们尚未实现生物方向酰胺烷基化的预期结果。尽管如此，我仍然希望继续探索新的反应机制和合成策略，最终会导致成功的成功。这个区域。此外，我认为从这些失败的尝试中获得的知识将证明在未来化学生物学技术和应用的发展中很有价值。总体而言，虽然寻找一种新的生物方向酰胺烷基化方法一直具有挑战性，但我仍然致力于推进该领域并为此问题开发创新的解决方案。