A propeller‐like small molecule as a novel G‐quadruplex DNA binder: The study of fluorescent sensing property and preferential interactions with human telo21 structure

Abstract

A new propeller-like small molecule was synthesized with three terminal amino side groups. The molecule was found to be a selective nucleic acid binder towards telo21 G-quadruplex DNA compared with other representative nucleic acids including single-stranded DNA (dA21), duplex DNA (ds26) and RNA. The fluorescent signal of the molecule upon interaction with telo21 G-quadruplex structure shows remarkable enhancement (F /F = 17.9) while interaction with other nucleic acids shows the signal enhancement which is less than 2.1. In addition, a good linear relationship of binding signal correlated with the concentration of telo21 DNA was obtained. Molecular docking study was also performed to acquire the binding behaviour and its interaction modes of the molecule with the structure of human telomeric DNA G-quadruplex. The modelling results show that the three conjugated terminal units (dimethylaminobenzyl groups) associated through the ethylene bridges with the central methylated pyridine ring formed a co-planar conformation upon stacking onto the G-quartets via pi-pi stacking interactions. This could be the key reason that the molecule shows excellent fluorescent signal of binding towards telo21 G-quadruplex DNA rather than other types of nucleic acids.

Lutidine derivatives for live-cell imaging of the mitochondria and endoplasmic reticulum

“…[26][27][28] Several lutidine derivatives have been utilized for biomolecular investigations: interactions with nucleic acids, proteins, and live-cell imaging applications. [29][30][31][32][33] Considering their lower toxicity, high signal-to-noise ratios, and a knowledge of their biomolecular interactions, we used 2,6-lutidine as a scaffold to target sub-cellular organelles. We systematically varied the substituents by incorporating methyl, benzyl, and polyfluorophenyl motifs: the substitutions contribute to the changes in lipophilicity and biomolecular affinity within the cell.…”

Structurally diverse G-quadruplexes as the noncanonical nucleic acid drug target for live cell imaging and antibacterial study

“…In an attempt to probe the crucial factors in rational design of G4-selective ligands, our group has developed several ligand systems. We found that, apart from adopting a planar core molecular fragment to construct G4-ligands, the overall molecular size, 116 symmetry, 117,118 flexibility, 83 and the character of terminal groups [119][120][121][122] may affect the in vitro selectivity of the ligand toward G4-structures against RNA, single-and double-stranded DNA. Our study suggests that some smallsized molecular scaffolds including benzothiazole-benzofuroquinolinium, 123,124 benzothiazole-indolium, 125 1-methylquinolinium, 126 thiazole orange 81,84,127 and benzo[e]indole 128 are good molecular fragments for the design of fluorescent G4-ligands to achieve high discrimination ability, sensitivity and quantum yield targeting certain types of G4s for in vitro sensing and live cell imaging.…”

Commentary: Reproducible science, why protocols matter

“…Commentary: Reproducible science, why protocols matter David L. Selwood F I G U R E 1 Detection of exon 2 deletion of AIMP2 based on split a G-quadruplex system, the chemical structure of NMM is shown on the right. Figure taken (Sun et al, 2018) and a second describes a novel fluorescent system for detection of genetic mutations but without using sequencing (Zang, Wang, Zhu, Yao, & Shi, 2018). This system is developed for detection of exon 2 deletion of AIMP2 which is thought to important in some cancers, such as ovarian and lung cancers.…”

“…The DNA and RNA system tools category highlights the increasing importance of this area to therapeutics, two papers on G‐quadruplex systems: one from Ning Sun and co‐workers (Wing‐Leung Wong lab.) describing a propeller‐like molecule as a probe (Sun et al., ) and a second describes a novel fluorescent system for detection of genetic mutations but without using sequencing (Zang, Wang, Zhu, Yao, & Shi, ). This system is developed for detection of exon 2 deletion of AIMP2 which is thought to important in some cancers, such as ovarian and lung cancers.…”