» Articles » PMID: 23909929

Solution Structure of an Intramolecular (3 + 1) Human Telomeric G-quadruplex Bound to a Telomestatin Derivative

Overview
Journal J Am Chem Soc
Specialty Chemistry
Date 2013 Aug 6
PMID 23909929
Citations 51
Authors
Affiliations
Soon will be listed here.
Abstract

Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.

Citing Articles

Complex Biophysical and Computational Analyses of G-Quadruplex Ligands: The Porphyrin Stacks Back.

Satta G, Trajkovski M, Cantara A, Mura M, Meloni C, Olla G Chemistry. 2024; 30(69):e202402600.

PMID: 39291646 PMC: 11632414. DOI: 10.1002/chem.202402600.


A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs.

Neidle S Molecules. 2024; 29(15).

PMID: 39125057 PMC: 11314571. DOI: 10.3390/molecules29153653.


G-Quadruplex Structure in the ATP-Binding DNA Aptamer Strongly Modulates Ligand Binding Activity.

Edwards A, Iannucci A, VanDenBerg J, Kesti A, Rice T, Sethi S ACS Omega. 2024; 9(12):14343-14350.

PMID: 38560010 PMC: 10976393. DOI: 10.1021/acsomega.3c10386.


BG4 antibody can recognize telomeric G-quadruplexes harboring destabilizing base modifications and lesions.

Johnson S, Paul T, Sanford S, Schnable B, Detwiler A, Thosar S Nucleic Acids Res. 2023; 52(4):1763-1778.

PMID: 38153143 PMC: 10939409. DOI: 10.1093/nar/gkad1209.


ASC-G4, an algorithm to calculate advanced structural characteristics of G-quadruplexes.

Farag M, Messaoudi C, Mouawad L Nucleic Acids Res. 2023; 51(5):2087-2107.

PMID: 36794725 PMC: 10018348. DOI: 10.1093/nar/gkad060.