Physicochemical Properties of the Phosphoryl Guanidine Oligodeoxyribonucleotide Analogs

Russian Journal of Bioorganic Chemistry - This work describes the basic physicochemical properties of phosphoryl guanidine oligonucleotides (PGOs)—a new type of DNA analog with a partially or...     

Study of the Staudinger Reaction and Reveal of Key Factors Affecting the Efficacy of Automatic Synthesis of Phosphoryl Guanidinic Oligonucleotide Analogs

Russian Journal of Bioorganic Chemistry - In this work, we introduce a novel nuanced analysis of the chemical transformations occurs during the automatic synthesis of phosphoryl guanidine...     

A convenient solid phase approach to obtain lipophilic 5′-phosphoramidate derivatives of DNA and RNA oligonucleotides

This paper explores the potential of a modified phosphotriester approach to the synthesis of 5′-phosphoramidate derivatives of DNA and RNA oligonucleotides. The modification of 5′-deprotected support-bound oligonucleotides is done in two steps: i) conversion of the 5′-OH group of an oligonucleotide into an activated phosphodiester, and ii) treatment of the activated phosphodiester with an aminocompound. The approach is efficient and compatible with conventional solid phase oligonucleotide synthesis. It can be used for the conjugation of therapeutically relevant oligonucleotides with functional moieties or carrier constructions, which are to be removed after endocytosis.     

Antiviral Activity of a New Class of Chemically Modified Antisense Oligonucleotides against Influenza А Virus

Russian Journal of Bioorganic Chemistry - The paper reports the synthesis of a series of antisense oligonucleotides (aONs) directed against different segments of the influenza A virus genome (H1N1)...     

A Comparative Study of the Hybridization of Phosphoryl Guanidine Oligonucleotides with DNA and RNA

Russian Journal of Bioorganic Chemistry - The structure and thermal stability of complexes of RNA and DNA with phosphoryl guanidine oligonucleotides (PGO) bearing modified phosphate residues in...     

Triazinylamidophosphate Oligonucleotides: Synthesis and Study of Their Interaction with Cells and DNA-Binding Proteins

Russian Journal of Bioorganic Chemistry - In this work, representatives of the class of triazinylamidophosphate oligonucleotide derivatives were obtained for the first time. A scheme for the...     

Oligonucleotide derivatives in nucleic acid hybridization analysis. III. Synthesis and investigation of properties of oligonucleotides, bearing bifunctional non-nucleotide insertion

Non-nucleotide phosporamidites were synthetized, having a branching backbone with different positions for functional groups. Phosphoramidite monomers obtained contain intercalator moiety, 6-chloro-2-methoxyacridine, and additional hydroxyl residue protected with dimethoxytrityl group or with the tert-butyldimethylsilyl group for post-synthetic modification. Oligothymidilates containing one or more modified units in different positions of the sequence were synthesized. The melting point and thermodynamic parameters of the formation of complementary duplexes formed by modified oligonucleotides were defined (change in enthalpy and entropy). The introduction of intercalating residue causes a significant stabilization of DNA duplexes. It is shown that the efficiency of the fluorescence of acridine residue in the oligonucleotide conjugate significantly changes upon hybridization with DNA.     

Pre-steady state kinetics of DNA binding and abasic site hydrolysis by tyrosyl-DNA phosphodiesterase 1

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) processes DNA 3′-end-blocking modifications, possesses DNA and RNA 3′-nucleosidase activity and is also able to hydrolyze an internal apurinic/apyrimidinic (AP) site and its synthetic analogs. The mechanism of Tdp1 interaction with DNA was analyzed using pre-steady state stopped-flow kinetics with tryptophan, 2-aminopurine and Förster resonance energy transfer fluorescence detection. Phosphorothioate or tetramethyl phosphoryl guanidine groups at the 3′-end of DNA have been used to prevent 3′-nucleosidase digestion by Tdp1. DNA binding and catalytic properties of Tdp1 and its mutants H493R (Tdp1 mutant SCAN1) and H263A have been compared. The data indicate that the initial step of Tdp1 interaction with DNA includes binding of Tdp1 to the DNA ends followed by the 3′-nucleosidase reaction. In the case of DNA containing AP site, three steps of fluorescence variation were detected that characterize (i) initial binding the enzyme to the termini of DNA, (ii) the conformational transitions of Tdp1 and (iii) search for and recognition of the AP-site in DNA, which leads to the formation of the catalytically active complex and to the AP-site cleavage reaction. Analysis of Tdp1 interaction with single- and double-stranded DNA substrates shows that the rates of the 3′-nucleosidase and AP-site cleavage reactions have similar values in the case of single-stranded DNA, whereas in double-stranded DNA, the cleavage of the AP-site proceeds two times faster than 3′-nucleosidase digestion. Therefore, the data show that the AP-site cleavage reaction is an essential function of Tdp1 which may comprise an independent of AP endonuclease 1 AP-site repair pathway.     

Algorithm for Searching and Testing the Activity of Antisense Oligonucleotides Exemplified by the mRNA of the rpoD Gene Encoding Staphylococcus aureus RNA Polymerase Sigma Factor

Russian Journal of Bioorganic Chemistry - One of the promising strategies in the development of efficient antibacterial drugs is the use of antisense oligonucleotides specifically interacting with...     

Oligonucleotide Functionalization by a Novel Alkyne-Modified Nonnucleosidic Reagent Obtained by Versatile Building Block Chemistry

A convenient synthetic strategy has been designed to prepare an alkyne-modified synthon for automated DNA synthesis. It is based on the key O-DMTr-protected 4-(2-hydroxyethyl)morpholin-2,3-dione and building blocks obtained by its functionalization by various aliphatic amines. A respective nonnucleosidic phosphoramidite monomer containing a terminal alkyne in the side-chain was synthesized, and corresponding oligothymidylates incorporating the modification in various positions were prepared. The presence of the alkyne group was confirmed by Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) between the functionalized oligonucleotide and an azide derivative of 7-nitro-2,1,3-benzoxadiazole.