Topological conversion of human telomeric G-quadruplexes from hybrid to parallel form induced by naphthalene diimide ligands.

Abstract:

:G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramolecular GQs. Here we report the topological conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K+ solution. The ligands selectively induce metastable hybrid-type GQs to highly stable parallel-type GQ at physiological temperature (37 °C) in dilute aqueous solutions and under crowding conditions that mimic cellular bioenvironment. According to spectroscopic analyses, the topological conversion is speculated to undergo stepwise unfolding of hybrid-type GQ through intermediate states to parallel-type GQ. The results will prompt further studies on the designs of ligands with GQ conformation regulation functions and nanotechnological systems based on nucleic acids with dynamic regulation of GQ conformation.

journal_name

Int J Biol Macromol

authors

Hao X,Wang C,Wang Y,Li C,Hou J,Zhang F,Kang C,Gao L

doi

10.1016/j.ijbiomac.2020.11.059

subject

Has Abstract

pub_date

2021-01-15 00:00:00

pages

1048-1058

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(20)34990-4

journal_volume

167

pub_type

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