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Synthesis of -Diketone DNA Derivatives for Affinity Modification of Proteins

Monakhova, M V and Kubareva, E A and Romanova, E A and Semkina, A S and Naberezhnov, DS and Rao, D N and Zatsepin, T S and Oretskaya, T S (2019) Synthesis of -Diketone DNA Derivatives for Affinity Modification of Proteins. In: RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY, 45 (2). pp. 144-154.

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Official URL: https://doi.org/10.1134/S1068162019020079


Diketone DNA derivatives have been proposed to modify the guanidine group of Arg in proteins. The -diketo group at the C2' atom of the sugar phosphate moiety has been introduced in DNA by acylation of oligonucleotide precursors, i.e., DNA fragments containing 2'-amino-2'-deoxyuridine, which have been synthesized by the chemical automatic synthesis. Water-soluble N-3-(dimethylamino)propyl]-N-ethylcarbodiimide (EDC) and 4,6-dioxoheptanoic acid have been used in the reaction. The ability of oligodeoxyribonucleotides containing the 2'--diketo group to react with guanidine, N-Boc-L-arginine, and N-Dns-L-arginine has been demonstrated. The introduction of this modification into one of the strands of the 15-base pair DNA duplex has been shown to lead to its destabilization. The conjugate formation of MutS and MutL proteins from the E.coli mismatch repair system with 17-base pair DNA duplexes containing the 2'-deoxy-2'-(4,6-dioxoheptylamido)uridine residue has been detected for the first time. To increase the selectivity of the DNA ligands containing the -diketo group in the reaction with the Arg residues of proteins, we have proposed to treat the reaction mixture with hydroxylamine. This treatment leads to the cleavage of Schiff bases, which are formed with the involvement of lysine residues.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to MAIK NAUKA/INTERPERIODICA/SPRINGER
Keywords: modified DNA; -diketo group; mismatch repair; MutS and MutL proteins; DNA-protein conjugates
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 25 Jun 2019 17:59
Last Modified: 25 Jun 2019 17:59
URI: http://eprints.iisc.ac.in/id/eprint/63087

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