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。目标是具有反应性氨基酸侧链部分，其在用光或反应物/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和相容的，以用于体外肽翻译和mRNA展示筛选平台RaPID。然而，尽管我们做了大量的努力，迄今为止，所提出的方法都没有被证明是成功的。此外，金属催化的交叉偶联，特别是利用Pd 0以及含CuI和CuII的催化剂，在水性条件下进行了测试。不幸的是，尽管这些反应方法的最初的承诺和许多迭代，我们还没有达到生物正交酰胺烷基化的预期结果，尽管这些挫折，我仍然希望，新的反应机制和合成策略的继续探索，最终将导致在这一领域的成功。此外，我相信从这些失败的尝试中获得的知识将证明对未来化学生物学技术和应用的发展有价值。总的来说，虽然寻找一种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的发展，并为这个问题开发创新的解决方案。

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.