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5‐Methylcytosine Substantially Enhances the Thermal Stability of DNA Minidumbbells
Author(s) -
Wan Liqi,
Yi Jie,
Lam Sik Lok,
Lee Hung Kay,
Guo Pei
Publication year - 2021
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.202005410
Subject(s) - 5 methylcytosine , cytosine , dna , thermal stability , melting temperature , base pair , chemistry , base (topology) , dna methylation , biochemistry , materials science , gene , organic chemistry , mathematical analysis , gene expression , mathematics , composite material
Minidumbbell (MDB) is a recently identified non‐B DNA structure that has been proposed to associate with genetic instabilities. It also serves as a functional structural motif in DNA nanotechnology. DNA molecular switches constructed using MDBs show instant and complete structural conversions with easy manipulations. The availability of stable MDBs can broaden their applications. In this work, we found that substitutions of cytosine with 5‐methylcytosine could lead to a significant enhancement in the thermal stabilities of MDBs. Consecutive methylations of cytosine in MDBs brought about cumulative stabilization with a drastic increase in the melting temperature by 23 °C. NMR solution structures of two MDBs containing 5‐methylcytosine residues have been successfully determined and revealed that the enhanced stabilities resulted primarily from favorable hydrophobic contacts, more stable base pairs and enhanced base‐base stackings involving the methyl group of 5‐methylcytosine.