i-Motif-Binding Ligands and Their Effects on the Structure and Biological Functions of i-Motif

Abstract

The i-motif is a high-order DNA structure formed by hemiprotonated cytosine-cytosine base pairs under acidic conditions. It is less well studied than other high-order DNA structures, such as G-quadruplexes. However, increasing numbers of i-motif-binding ligands are being reported, and they are being used as tools to investigate the i-motif's structure and biological functions. It has become clear that the i-motif has a functional role in the regulation of gene expression. In this review, we provide an overview of i-motif ligands so far reported, and we summarize their effects on the structure and their use as tools to investigate its biological functions.

Dynamics Studies of DNA with Non-canonical Structure Using NMR Spectroscopy

“…The discovery and design of i-motif binding ligands is not well developed due to the fact that its formation occurs in acidic pH in vitro [76]. Starting with TMPyP4 [83] and BisA [84], a few ligands that can bind to i-motifs have been described [76,85]. Among them, a study on ligands for the C-rich DNA sequence of the human B-cell lymphoma gene-2 (BCL2) promoter region is relatively well described [86].…”

“…Actually, the shifting of the equilibrium in one direction by the ligands occurred in vivo, during their regulation of the expression of the BCL2 gene. that can bind to i-motifs have been described [76,85]. Among them, a study on ligands for the C-rich DNA sequence of the human B-cell lymphoma gene-2 (BCL2) promoter region is relatively well described [86].…”

Selection and application of aptamers with high-affinity and high-specificity against dinophysistoxin-1

“…† At the present stage, the special secondary structure such like stem-loop, bulge, pseudoknot and three-way helix structure, might mainly lead to the binding affinity. 43 Based on this, we further cut off the stem loop A or B of N59 based on the secondary structure to obtain variants N59b, N59c.…”

Unraveling the Regulatory G-Quadruplex Puzzle: Lessons From Genome and Transcriptome-Wide Studies

“…The cross-reactivity between G4 ligands and i-motifs has also been reported since i-motifs are present on the opposite strand of the G4. Ligands such as TMPyP4 and berberine were shown to bind to i-motifs, although their ability to stabilize them was lower than that of G4s (Fedoroff et al, 2000; Masoud and Nagasawa, 2018; Pagano et al, 2018). The prevalence of G4s in the RNA has also been shown recently (Kwok et al, 2016; Yang et al, 2018), and the functional effects of RNA G4 stabilization have also been reviewed before (Fay et al, 2017).…”