新加坡国立大学Ru-Yi Zhu团队报道了将DNA修复与生物正交缀合物融合实现不对称DNA催化的通用性合成。相关研究成果于2024年6月11日发表在《美国化学会杂志》。

由于难以及时组装催化剂类似物库，因此通过高通量筛选不对称催化来优化催化剂具有挑战性。

该文中，研究人员重新利用DNA切除修复，并将其与生物正交缀合相结合，构建了一系列不同的DNA杂化催化剂，用于高可及性和高通量的不对称DNA催化，从而大大加快了催化剂优化过程，获得了优异的反应性和选择性，以及第一个阻反选择性DNA催化。

这种偶联策略的生物正交性确保了对不同官能团的特殊耐受性，从而促进了携带各种未保护官能团的44种DNA杂化催化剂的容易构建。这一独特特征有可能在不对称DNA催化中实现以前认为无法实现的催化模式。

附：英文原文

Title: Merging DNA Repair with Bioorthogonal Conjugation Enables Accessible and Versatile Asymmetric DNA Catalysis

Author: Jie Sheng, Zhaoyang Li, Kelly Kar Yun Koh, Qi Shi, Angel Foo, Philip Mark Leetiong Tan, Tuan-Khoa Kha, Xujie Wang, Leonard Fang, Ru-Yi Zhu

Issue&Volume: June 11, 2024

Abstract: Optimizing catalysts through high-throughput screening for asymmetric catalysis is challenging due to the difficulty associated with assembling a library of catalyst analogues in a timely fashion. Here, we repurpose DNA excision repair and integrate it with bioorthogonal conjugation to construct a diverse array of DNA hybrid catalysts for highly accessible and high-throughput asymmetric DNA catalysis, enabling a dramatically expedited catalyst optimization process, superior reactivity and selectivity, as well as the first atroposelective DNA catalysis. The bioorthogonality of this conjugation strategy ensures exceptional tolerance toward diverse functional groups, thereby facilitating the facile construction of 44 DNA hybrid catalysts bearing various unprotected functional groups. This unique feature holds the potential to enable catalytic modalities in asymmetric DNA catalysis that were previously deemed unattainable.

DOI: 10.1021/jacs.4c03210

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c03210