Department of Chemistry, UNIST (Ulsan National Institute of Science & Technology), Ulsan, Korea.
Nat Commun. 2021 Mar 16;12(1):1681. doi: 10.1038/s41467-021-21839-4.
Site-selective modification of oligonucleotides serves as an indispensable tool in many fields of research including research of fundamental biological processes, biotechnology, and nanotechnology. Here we report chemo- and regioselective modification of oligonucleotides based on rhodium(I)-carbene catalysis in a programmable fashion. Extensive screening identifies a rhodium(I)-catalyst that displays robust chemoselectivity toward base-unpaired guanosines in single and double-strand oligonucleotides with structurally complex secondary structures. Moreover, high regioselectivity among multiple guanosines in a substrate is achieved by introducing guanosine-bulge loops in a duplex. This approach allows the introduction of multiple unique functional handles in an iterative fashion, the utility of which is exemplified in DNA-protein cross-linking in cell lysates.
寡核苷酸的位点选择性修饰是许多研究领域（包括基础生物过程研究、生物技术和纳米技术）不可或缺的工具。在这里，我们报告了基于铑（I）-卡宾催化的寡核苷酸的化学和区域选择性修饰，这种修饰是可编程的。广泛的筛选确定了一种铑（I）催化剂，它对具有复杂二级结构的单链和双链寡核苷酸中未配对的鸟嘌呤具有强大的化学选择性。此外，通过在双链体中引入鸟嘌呤凸起环，可以在底物中实现多个鸟嘌呤之间的高区域选择性。这种方法允许以迭代的方式引入多个独特的功能接头，其在细胞裂解物中的 DNA-蛋白质交联中的应用实例证明了其用途。
