Direct Conjugation of Peptides and 5-Hydroxymethylcytosine in DNA

被引:3
|
作者
Serva, Saulius [1 ,2 ]
Lagunavicius, Arunas [1 ]
机构
[1] Thermo Fisher Sci Balt, LT-02241 Vilnius, Lithuania
[2] Vilnius State Univ, Fac Nat Sci, Dept Biochem & Mol Biol, LT-03101 Vilnius, Lithuania
关键词
OLIGONUCLEOTIDES; 5-METHYLCYTOSINE; STRATEGIES; CONVERSION; DATABASE;
D O I
10.1021/acs.bioconjchem.5b00165
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Recent discovery of functional 5-hydroxymethylcytosine in vertebrate genomes prompted for elaboration of methods to localize this modification at the nucleotide resolution level. Among several covalent modification-based approaches, atypical activity of cytosine-5 DNA methyl-transferases to couple small molecules to 5-hydroxymethylcytosine stands out for acceptance of broad range of ligands. We went further to explore the possibility for methyltransferase-maintained coupling of compounds possessing autonomous functions. Functionalization of DNA was achieved by direct conjugation of chemically synthesized peptides of regular structure. Sequence, residue, and position-specific coupling of DNA containing 5-hydroxymethylcytosine and different peptides has been demonstrated, with the nature of the resulting conjugates confirmed by protease treatment and mass spectrometry. Coupling products were compatible with affinity-driven separation from the unmodified DNA. This approach highlights an emerging avenue toward the enzymatic, sequence-specific DNA functionalization, enabling a single step merge of the DNA and peptide moieties into a bifunctional entity.
引用
收藏
页码:1008 / 1012
页数:5
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