Probing Synergistic Effects of DNA Methylation and 2--Fluorination on i-Motif Stability

被引：16

作者：

Abou Assi, Hala ^{[1
]}

Lin, Yu Chen ^{[1
]}

Serrano, Israel ^{[2
]}

Gonzalez, Carlos ^{[2
]}

Damha, Masad J. ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, 801 Sherbrooke St West, Montreal, PQ H3A 0B8, Canada

[2] CSIC, Inst Quim Fis Rocasolano, Serrano 119, E-28006 Madrid, Spain

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2018年 / 24卷 / 02期

基金：

加拿大自然科学与工程研究理事会;

关键词：

biological chemistry; 5-methylcytosine; epigenetic modifications; nucleosides; telomeric DNA; G-QUADRUPLEX; CARBON NANOTUBES; GENE-EXPRESSION; CYTOSINE; OLIGONUCLEOTIDES; 5-METHYLCYTOSINE; STABILIZATION; TELOMERASE; FRAGMENT; COMPLEX;

D O I：

10.1002/chem.201704591

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 (2F-araC), and 2-deoxy-2-fluoro-5-methyl-arabinocytidine (5-Me-2F-araC). The base pair 5-Me-2F-araC:2F-araC produced i-motifs with a pH(1/2) (pK(a)) value that closely matches physiological pH (7.34 +/- 0.3). NMR analysis of the most stable telomeric sequence (HJ-2) at pH7.0 indicated that the structure is stabilized by hybrid 5-Me-dC:2F-araC hemiprotonated base pairs and therefore highlights the significance of the interplay between base and sugar modifications on the stability of i-motif structures.

引用

页码：471 / 477

页数：7

共 52 条

[1] Stabilization of i-motif structures by 2′-β-fluorination of DNA [J].