Direct conjugation of peptides and 5-hydroxymethylcytosine in DNA
| Autor: | Saulius Serva, Arunas Lagunavicius |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Methyltransferase DNA-Cytosine Methylases Spiroplasma Biomedical Engineering Pharmaceutical Science Bioengineering Sequence (biology) Genome chemistry.chemical_compound Residue (chemistry) Cytosine Nucleotide Amino Acid Sequence Pharmacology chemistry.chemical_classification 5-Hydroxymethylcytosine Organic Chemistry DNA Small molecule chemistry Biochemistry 5-Methylcytosine Peptides Biotechnology |
| Zdroj: | Bioconjugate chemistry. 26(6) |
| ISSN: | 1520-4812 |
| Popis: | 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 methyltransferases 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. |
| Databáze: | OpenAIRE |
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