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

TitleDramatic effect of furanose C2’ substitution on structure and stability: directing the folding of the human telomeric quadruplex with a single fluorine atom.
Publication TypeJournal Article
Year of Publication2013
AuthorsMartín-Pintado, Nerea, Yahyaee-Anzahaee Maryam, Deleavey Glen F., Portella Guillem, Orozco Modesto, Damha Masad J., and González Carlos
JournalJ Am Chem Soc
Volume135
Pagination5344-7
Date Published2013 Apr 10
ISSN1520-5126
KeywordsArabinose, DNA, Fluorine, G-Quadruplexes, Humans, Models, Molecular, Molecular Structure, Protein Folding, Telomere
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.
DOI10.1021/ja401954t