Ligand Design to Acquire Specificity to Intended G‐Quadruplex Structures

Abstract

A G-quadruplex is a nucleic acid secondary structure that is adopted by guanine-rich sequences, and is considered to be relevant in various pharmacological and biological contexts. G-Quadruplexes have also attracted great attention in the field of DNA nanotechnology because of their extremely high thermal stability and the availability of many defined structures. To date, a large repertory of DNA/RNA G-quadruplex-interactive ligands has been developed by numerous laboratories. Several relevant reviews have also been published that have helped researchers to grasp the full scope of G-quadruplex research from its outset to the present. This review focuses on the G-quadruplex ligands that allow targeting of specific G-quadruplexes. Moreover, unique ligands, successful methodologies, and future perspectives in relation to specific G-quadruplex recognition are also addressed.

Specific Binding of a d‐RNA G‐Quadruplex Structure with an l‐RNA Aptamer

“…In this work, we found that our l ‐RNA aptamer, l ‐Ap3‐7, contains an rG4, which is new and interesting. l ‐Ap3‐7’s affinity ( K d ≈100 n m ) is weaker than the G4‐specific antibody BG4 that has a sub‐n m K d , but is comparable to most G4‐specific ligands . Moreover, its ability to distinguish between G4s is encouraging, although we cannot rule out the possibility that it may have some off‐target effect.…”

The diverse structural landscape of quadruplexes

“…The diversity of quadruplex structures will widen with improved methods for detection and evaluation. Such structures will likely change the face of small molecule‐quadruplex targeting as a therapeutic intervention strategy ; these novel RNA structures would likely be exploitative in drug discovery.…”

An Octahedral Cobalt(III) Complex with Axial NH3 Ligands that Templates and Selectively Stabilises G‐quadruplex DNA

“…A large proportion of G4 DNA binders reported to date have been designed to interact with the external tetrads of G4s via a combination of π–π stacking and electrostatic interactions . Therefore, most G4 binders are planar molecules containing two or more aromatic rings that display strong π–π interactions with the guanine tetrads.…”

“…Al arge proportion of G4 DNA bindersr eported to date have been designed to interact with the external tetrads of G4s via ac ombination of p-p stacking and electrostatic interactions. [9,10] Therefore, most G4 bindersare planar molecules con- taining two or more aromatic rings that display strong p-p interactions with the guanine tetrads. In addition, most of these compounds also feature substituents with positive charges which increase their affinity for the negatively charged DNA.…”