Protein-DNA interactions are involved in many crucial biological processes (transcription, replication repair etc.). Covalent cross-linking of the binding proteins with reactive DNA probes is a promising method to identify and study these interactions. It may be also useful for other applications in chemical biology or targeting of therapeutic nucleic acids.
Therefore, scientists are looking for new efficient bioconjugation and cross-linking methods, in particular reactive groups specific for certain amino acid side-chains.
Following their previous works that addressed cross-linking with Cys, His, and Lys, in their new work, Michal Hocek and his group at IOCB Prague focused on arginine, a nucleophilic amino acid often present in DNA-binding proteins.
They prepared a nucleotide bearing reactive 1,3-diketone function which reacts with arginine under physiological conditions forming stable pyrimidine moiety. The modified nucleotide was used for enzymatic synthesis of reactive DNA probes that cross-linked with Arg-containing peptides and proteins (e.g. histones).
The team published their results in Angewandte Chemie with Denise-Liu' Leone as the first author.
Read the paper:
- Leone, D.-L., Hubálek, M., Pohl, R., Sýkorová, V. and Hocek, M. (2021), 1,3-Diketone-Modified Nucleotides and DNA for Cross-Linking with Arginine-Containing Peptides and Proteins. Angew. Chem. Int. Ed. https://doi.org/10.1002/anie.202105126
