Synthesis of β-Diketone DNA Derivatives for Affinity Modification of Proteins
- Authors: Monakhova M.V.1, Kubareva E.A.1, Romanova E.A.1, Semkina A.S.2, Naberezhnov D.S.3, Rao D.N.4, Zatsepin T.S.5, Oretskaya T.S.1
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Affiliations:
- Chemistry Department and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University
- Pirogov Russian National Research Medical University
- Blokhin National Medical Research Center of Oncology, Ministry of Health
- Department of Biochemistry, Indian Institute of Science
- Skolkovo Institute of Science and Technology
- Issue: Vol 45, No 2 (2019)
- Pages: 144-154
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229177
- DOI: https://doi.org/10.1134/S1068162019020079
- ID: 229177
Cite item
Abstract
Diketone DNA derivatives have been proposed to modify the guanidine group of Arg in proteins. The β-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'-β-diketo group to react with guanidine, Nα-Boc-L-arginine, and Nα-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 β-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.
About the authors
M. V. Monakhova
Chemistry Department and Belozersky Institute of Physico-Chemical Biology,Lomonosov Moscow State University
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 119991
E. A. Kubareva
Chemistry Department and Belozersky Institute of Physico-Chemical Biology,Lomonosov Moscow State University
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 119991
E. A. Romanova
Chemistry Department and Belozersky Institute of Physico-Chemical Biology,Lomonosov Moscow State University
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 119991
A. S. Semkina
Pirogov Russian National Research Medical University
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 117997
D. S. Naberezhnov
Blokhin National Medical Research Center of Oncology, Ministry of Health
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 115478
D. N. Rao
Department of Biochemistry, Indian Institute of Science
Email: oretskaya@belozersky.msu.ru
India, Bangalore, 560012
T. S. Zatsepin
Skolkovo Institute of Science and Technology
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 121205
T. S. Oretskaya
Chemistry Department and Belozersky Institute of Physico-Chemical Biology,Lomonosov Moscow State University
Author for correspondence.
Email: oretskaya@belozersky.msu.ru
Russian Federation, Moscow, 119991