title: Development of a highly sensitive fluorescent light-up probe for G-quadruplexes.
abstract: G-quadruplexes are higher-order nucleic acid structures that have attracted extensive attention because of their biological significance and potential applications in supramolecular chemistry. An ever-increasing interest in G-quadruplexes has promoted the development of selective and sensitive fluorescent probes as research tools for these structures. However, most current studies primarily focus on the improved selectivity of probes for G-quadruplexes. Their detection limits or ways to improve their detection limits are rarely described. In this study, a new set of di-substituted triarylimidazole fluorescent probes were designed and synthesized, with the aim of upgrading the detection limit of a lead triarylimidazole IZCM-1 for G-quadruplexes. Among these compounds, IZCM-7 was the most promising candidate. The limit of detection (LOD) value of IZCM-7 for the G-quadruplex was up to 3 nM in solution and up to 5 ng in a gel matrix. These values were significantly improved in comparison with those of IZCM-1. Further biophysical studies revealed that the fluorescence quantum yield and binding affinity of IZCM-7 for G-quadruplexes were markedly increased, and these two factors might be responsible for the significantly improved detection limit of IZCM-7. In addition, the sensitive and selective fluorescence performance of IZCM-7 for G-quadruplexes remained the same even in the presence of large amounts of non-G-quadruplex competitors, suggesting its promising application prospect.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. tanjiah@mail.sysu.edu.cn.
authors.forename: Ming-Hao
authors.initials: MH
authors.lastname: Hu
authors.forename: Shuo-Bin
authors.initials: SB
authors.lastname: Chen
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Guo
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000235:genetics; D015195:Drug Design; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D054856:G-Quadruplexes; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry; D057230:Limit of Detection; D056004:Molecular Dynamics Simulation; D055620:Optical Phenomena; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D007093:Imidazoles; D004247:DNA