特殊ペプチド・フォールダマーハイブリッド分子の研究

在过去的一年里，我一直致力于开发一种新的生物正交分子内酰胺烷基化方法。目标是拥有一个反应性氨基酸侧链部分，在用光或反应物/催化剂活化后，可以环化到相邻的酰胺氮上。反应条件必须是生物正交的并且兼容用于体外肽翻译和 mRNA 显示筛选平台 RaPID。然而，尽管我们付出了巨大的努力，迄今为止所提出的方法都没有被证明是成功的。研究了几种不同的方法，包括二氮丙啶和含芴醇化合物的光化学活化。此外，在水性条件下测试了金属催化的交叉偶联，特别是使用 PdO 以及含 CuI 和 CuII 的催化剂。不幸的是，尽管这些反应方法有最初的承诺和多次迭代，但我们尚未实现生物正交酰胺烷基化的预期结果。尽管有这些挫折，我仍然希望不断探索新的反应机制和合成策略最终将在该领域取得成功。此外，我相信从这些失败的尝试中获得的知识将在未来化学生物学技术和应用的发展中证明是有价值的。总的来说，虽然寻找新的生物正交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开发针对该问题的创新解决方案。

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.