Premium
Probing Synergistic Effects of DNA Methylation and 2′‐β‐Fluorination on i‐Motif Stability
Author(s) -
Abou Assi Hala,
Lin Yu Chen,
Serrano Israel,
González Carlos,
Damha Masad J.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704591
Subject(s) - cytidine , chemistry , dna , base pair , methylation , sequence motif , telomere , cytosine , motif (music) , dna methylation , stereochemistry , biochemistry , gene , enzyme , gene expression , physics , acoustics
The possible role of DNA i‐motif structures in telomere biology and in the transcriptional regulation of oncogene promoter regions is supported by several recent studies. Herein we investigate the effect of four cytidine nucleosides (and combinations thereof) on i‐motif structure and stability, namely 2′‐deoxycytidine (dC), 2′‐deoxy‐5‐methyl‐cytidine (5‐Me‐dC), 2′‐deoxy‐2′‐fluoro‐arabinocytidine (2′F‐araC), and 2′‐deoxy‐2′‐fluoro‐5‐methyl‐arabinocytidine (5‐Me‐2′F‐araC). The base pair 5‐Me‐2′F‐araC:2′F‐araC produced i‐motifs with a pH 1/2 (“p K a ”) value that closely matches physiological pH (7.34±0.3). NMR analysis of the most stable telomeric sequence (HJ‐2) at pH 7.0 indicated that the structure is stabilized by hybrid 5‐Me‐dC:2′F‐araC hemiprotonated base pairs and therefore highlights the significance of the interplay between base and sugar modifications on the stability of i‐motif structures.