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。目标是得到一种反应性氨基酸侧链部分，当用光或反应物/催化剂活化时，可以环化到邻近的酰胺氮上。反应条件必须是生物正交性和相容的，才能用于体外多肽翻译和mRNA快速展示筛选平台。然而，尽管我们进行了广泛的努力，但到目前为止，还没有一种建议的方法被证明是成功的。我们研究了几种不同的方法，包括二氮杂环丙烷和荧醇化合物的光化学活化。此外，还测试了金属催化的交叉偶联反应，特别是在水相条件下使用Pd0以及含CuI和CuII的催化剂。不幸的是，尽管这些反应方法有了最初的希望和多次迭代，但我们还没有达到生物正交酰胺烷基化的预期结果。尽管有这些挫折，我仍然希望继续探索新的反应机理和合成策略，最终将在这一领域取得成功。此外，我相信从这些失败的尝试中获得的知识将被证明对未来化学生物学技术和应用的发展是有价值的。总体而言，虽然寻找一种新的生物正交酰胺烷基化方法具有挑战性，但我仍然致力于推动该领域的发展，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.