开发一种选择性配体，用于诱导 CGG 重复 RNA 中 G-G 错配的 RNA 结构转换，从 G-四链体到发夹样结构。

Development of a selective ligand for G-G mismatches of CGG repeat RNA inducing the RNA structural conversion from the G-quadruplex into a hairpin-like structure.

机构信息

Graduate School of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis ten bosch machi, Sasebo 859-3298, Japan.

Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.

出版信息

Org Biomol Chem. 2022 Apr 20;20(16):3375-3381. doi: 10.1039/d2ob00279e.

DOI:10.1039/d2ob00279e

PMID:35355034

Abstract

The trinucleotide CGG repeat is located in the 5'-UTR of and its abnormal expansion and formation of a noncanonical RNA structure causes fetal genetic diseases. In this study, a small molecular dimer-type ligand consisting of dual G-clamp units for the recognition of two neighboring guanines was synthesized, and the binding properties for the r(CGG) repeats were investigated. Compound 2 was confirmed to bind to the mismatch guanines in the stem region of the r(CGG) repeat hairpin. In addition, the RNase T1 assay demonstrated that 2 induced the structural conversion of the r(CGG) repeat from the G-quadruplex into a hairpin-like structure.

摘要

三核苷酸 CGG 重复序列位于的 5'-UTR 中，其异常扩增并形成非 canonical RNA 结构会导致胎儿遗传性疾病。在本研究中，设计并合成了一种小分子二聚体配体，该配体由两个识别两个相邻鸟嘌呤的 G 夹单元组成，并研究了其与 r(CGG) 重复序列的结合特性。实验证实，化合物 2 可以与 r(CGG) 重复发夹结构的茎环区域中的错配鸟嘌呤结合。此外，RNase T1 实验表明，2 诱导 r(CGG) 重复序列从 G-四链体结构向发夹样结构的构象转换。