O-フタルアルデヒド基を用いたペプチドの高効率マクロ環化とその応用

从2022年10月到2023年3月，我们的目标是研究基于OPA的技术，利用FIT系统构建非标准环肽库。由于OPA的高反应性，我们首先探索了3，4-THDA，一种反应性较低的二醛化合物。我们的实验证明了与赖氨酸和硫醇催化的硫代吡咯的选择性环化反应。与已报道的OPA化学方法相比，该方法具有更好的转化率和稳定性，但体外翻译的苛刻条件需要优化。我们还致力于OPA-CME衍生物的研究，用于Flexizyme介导的OPA酰化tRNA合成，旨在创建非标准文库。正在开发OPAON/OFF方法来控制翻译和翻译后环化过程中的OPA反应性。这一策略有助于识别针对结合口袋中含有半胱氨酸和赖氨酸残基的蛋白激酶的多肽抑制剂。

From Oct 2022 to Mar 2023, we aimed to investigate OPA-based technology for constructing nonstandard cyclic peptide libraries using FIT system. Due to OPA's high reactivity, we first explored 3,4-ThDA, a di-aldehyde compound with lower reactivity. Our experiments demonstrated selective cyclization with lysine and thiol-catalyzed thienopyrrole formation. This method yielded good conversion and better stability than the reported OPA chemistry, but the harsh conditions need optimization for in vitro translation.We are also working on OPA-CME derivatives for flexizyme-mediated OPA-acylated tRNA synthesis, aiming to create non-standard libraries. The OPAon/off method is being developed for controlling OPA reactivity during translation and post-translational cyclization. This strategy helps identify peptide inhibitors targeting protein kinases containing cysteine and lysine residues in the binding pockets.