Dramatic effect of furanose C2' substitution on structure and stability: directing the folding of the human telomeric quadruplex with a single fluorine atom

Nerea Martín-Pintado; Maryam Yahyaee-Anzahaee; Glen F Deleavey; Guillem Portella; Modesto Orozco; Masad J Damha; Carlos González

doi:10.1021/ja401954t

Dramatic effect of furanose C2' substitution on structure and stability: directing the folding of the human telomeric quadruplex with a single fluorine atom

J Am Chem Soc. 2013 Apr 10;135(14):5344-7. doi: 10.1021/ja401954t. Epub 2013 Mar 27.

Authors

Nerea Martín-Pintado¹, Maryam Yahyaee-Anzahaee, Glen F Deleavey, Guillem Portella, Modesto Orozco, Masad J Damha, Carlos González

Affiliation

¹ Instituto de Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain.

PMID: 23521511
DOI: 10.1021/ja401954t

Abstract

Human telomeric DNA quadruplexes can adopt different conformations in solution. We have found that arabinose, 2'F-arabinose, and ribose substitutions stabilize the propeller parallel G-quadruplex form over competing conformers, allowing NMR structural determination of this particularly significant nucleic acid structure. 2'F-arabinose substitution provides the greatest stabilization as a result of electrostatic (F-CH---O4') and pseudo-hydrogen-bond (F---H8) stabilizing interactions. In contrast, 2'F-rG substitution provokes a dramatic destabilization of the quadruplex structure due to unfavorable electrostatic repulsion between the phosphate and the 2'-F.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arabinose / chemistry*
DNA / chemistry*
Fluorine / chemistry*
G-Quadruplexes*
Humans
Models, Molecular
Molecular Structure
Protein Folding
Telomere / chemistry*

Substances

Fluorine
DNA
Arabinose