文献类型：期刊文献

中文题名：结核分枝杆菌Rv0341G4结合小分子活性化合物的筛选及初步验证

英文题名：Screening and Preliminary Validation of Small Molecules Binding to Mycobacterium tuberculosis Rv0341G4

作者：王昱斌[1];都甜甜[2];颉亚辉[3];潘云燕[1]

第一作者：王昱斌

机构：[1]兰州大学第二医院(第二临床医学院)检验医学中心,甘肃兰州730030;[2]兰州大学第二医院(第二临床医学院)肾病科,甘肃兰州730030;[3]甘肃中医药大学公共卫生学院,甘肃兰州730030

第一机构：兰州大学第二医院(第二临床医学院)检验医学中心,甘肃兰州730030

年份：2025

卷号：56

期号：7

起止页码：886

中文期刊名：中国医药工业杂志

外文期刊名：Chinese Journal of Pharmaceuticals

基金：甘肃省青年科技基金项目(21JR11RA115);甘肃省教育厅2023高校教师创新基金项目(2023B-104);临床萃英拔尖项目(CY2023-RJ-08)。

语种：中文

中文关键词：结核分枝杆菌;圆二色谱;Rv0341基因G4结构;表面等离子体共振;实时荧光定量反转录PCR;蛋白质印迹;抗结核药

外文关键词：Mycobacterium tuberculosis;circular dichroism spectroscopy;G-quadruplex structure within the Rv0341 gene;surface plasmon resonance;real time fluorescent quantitative reverse transcription polymerase chain reaction;Western blot;antituberculotic drug

摘要：该研究筛选了能特异性结合和稳定结核分枝杆菌Rv0341基因G4结构的小分子化合物。采用圆二色谱法探究Rv0341上富G寡核苷酸链能否形成G4(Rv0341G4)结构,并采用实时荧光定量反转录聚合酶链反应(qRT-PCR)和蛋白质印迹法验证小分子化合物对Rv0341表达的抑制作用。通过表面等离子体共振(SPR)技术筛选得与Rv0341G4结合的小分子化合物T-007;qRT-PCR法和蛋白质印迹法分析显示T-007可稳定Rv0341G4结构,对Rv0341转录具有负调控作用。该研究可为靶向GR结构的结核病治疗药物开发提供一定参考。
This study screened small molecule compounds capable of specifically binding to and stabilizing the G-quadruplex(G4)structure within the Rv0341 gene of Mycobacterium tuberculosis.Firstly,circular dichroism(CD)spectroscopy was used to confirm the formation of the G4 structure(designated Rv0341G4)by the G-rich oligonucleotide sequence in Rv0341 gene.Subsequently,real time fluorescent quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were employed to validate the inhibitory effects of candidate small molecules on Rv0341 expression.Through surface plasmon resonance(SPR)screening,a small molecule compound T-007 exhibiting high-affinity binding to Rv0341G4 was identified.Both qRT-PCR and Western blot analyses demonstrated that T-007 stabilizes the Rv0341G4 structure and downregulates Rv0341 transcription.This study provides valuable insights for developing novel anti-tuberculosis therapeutics targeting G4 structures.