[Acyclic nucleoside analogues. III. Synthesis of new 2',3'-dideoxy-2',3'-didehydronucleoside analogues]. / Atsiklicheskie analogi nukleozidov III. Sintez novykh atsiklicheskikh analogov 2'3'-didezoksi-2',3'-didegidronukleozidov.

The coupling of 5-acetoxy-1,1-dimethoxypent-2-ene with cytosine and thymine trimethylsilyl derivatives, as well as the reaction of 5-acetoxy-1-bromopent-2-ene with adenine sodium salt, yielded acyclic analogues of the corresponding nucleosides containing 5'-acetoxy groups. They were deprotected with a saturated methanolic solution of ammonia to the target analogues of nucleosides, which were characterized with 1H NMR, IR, and UV spectra. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 6; see also http://www.maik.ru.

[Synthesis of nucleoside analogs containing a cis-2-pentene fragment and their triphosphates]. / Sintez analogov nukleozidov, soderzhashchikh tsis-2-pentenovyi fragment, i ikh trifosfatov.

Acyclic analogs of thymidine, adenine, and cytosine where the ribose moiety is replaced with cis-5-hydroxypenthene, were obtained via condensation of cis-5-acetoxy-1-bromo-2-pentene with nucleic acid bases. Triphosphate derivatives of the new nucleosides were also synthesized to evaluate their action as terminators of DNA synthesis catalyzed by DNA polymerases.

[Synthesis and properties of DNA-duplexes, containing 9-(1'-hydroxy-2'-(hydroxymethyl)ethoxy)methylguanine]. / Sintez i svoistva DNK-dupleksov, soderzhashchikh 9-(1'-gidroksi-2'-(gidroksimetil)étoksi)metilguanin.

Phosphoramidite derivative of 9-[1'-hydroxy-2'-(hydroxymethyl)ethoxy]methylguanine (glG) is synthesized which allows one to introduce point modifications in any position of the chemically prepared oligonucleotide chain. Oligonucleotides with 5'-terminal glG can be used in chemical ligation promoted by cyanogen bromide. The modified oligonucleotide duplexes were characterized by melting curves and CD spectra.

Structural and kinetic aspects of chemical reactions in DNA duplexes. Information on DNA local structure obtained from chemical ligation data.

Chemical ligation of oligonucleotides in double-stranded helices has been considered in its structural-kinetic aspect. A study was made of (i) two series of DNA duplexes with various arrangements of reacting groups in the ligation junction induced by mispairing or by alteration of furanose structure (the replacement of dT unit with rU, aU, IU, xU, dxT ones) and of (ii) eight synthetic water-soluble carbodiimides with different substituents at N1 and N3 atoms. We assumed that some information on the local structure of modified sites in the duplex can be obtained from kinetic parameters of oligonucleotide coupling reaction. The ratio of kinetic constants k3/(k2 + k3) for productive and nonproductive decomposition of the activated phosphomonoester derivative apparently reflects the reaction site structure: for a given duplex this parameter is virtually independent of the condensing agent composition. Based on the analysis of the chemical ligation kinetics a suggestion has been made about the conformation of some modified units in the double helix.

Acyclic analogs of dideoxydidehydronucleosides.

A new type of acyclic nucleoside analogs is proposed, containing C5 hydroxyalkyl fragments, where the distance between 5'-hydroxyl group and the heterocyclic moiety corresponds to that in dideoxydidehydronucleosides (as confirmed by computer modelling). Condensation between 5-0-acetyl-1-bromo-2-pentene and persilylated heterocyclic bases (pyrimidines and guanine) or adenine sodium salt gives rise to the acyclic nucleosides (5a-d, 6a-d) with the yields ranging from 40% up to 85%. Deprotection by NH3/MeOH results in the desired nucleosides (1a-d, 2a-d) formation.

[Mutagenesis, directed by artificial oligonucleotide analogs. I. Participation of ribonucleotide fragments in DNA replication and repair]. / Mutagenez, napravlennyi neprirodnymi analogami oligonukleotidov. I. Uchastie ribonukleotidnykh zven'ev v reparatsii i replikatsii DNK.

The mutation system has been developed to study the mutagenic properties of modified oligonucleotide analogs. The mutagenic properties of oligonucleotides containing one ribonucleotide have been examined. The presence of a ribonucleotide is shown not to induce any mutations. But when the oligonucleotide induces two marker deletions detached by 6 nucleotides they may be repaired separately, in this case the deletion bordering with the ribonucleotide is predominantly repaired.

[Chemical reactions in double-helical nucleic acids. X. Kinetics of oligomer condensation under the effect of synthetic water-soluble carbodiimides]. / Khimicheskie reaktsii v dvuspiral'nykh nukleinovykh kislotakh. X. Kinetika kondensatsii oligomerov pod deistviem sinteticheskikh vodorastvorimykh karbodiimidov.

Chemical ligation of oligonucleotides in double stranded complexes has been considered in its structural-kinetic aspect. In a study of the reactivity of eleven synthetic water soluble carbodiimides the reaction rate has been found to be strongly affected by the substituents at N1 and N3 atoms. The chemical ligation appears to involve the linear form of carbodiimide. Model systems have been used to assess the rate constant for the phosphate activation. The ratio of kinetic constants for the productive and nonproductive reactions of the activated derivate apparently reflects the reactive site conformation; for a given duplex this parameter is virtually independent of the condensing agent structure.

[Chemical reactions of double-helical nucleic acids. XI. Interaction between kinetic parameters of chemical ligation in modified DNA-duplexes and structure of the reaction site]. / Khimicheskie reaktsii v dvuspiral'nykh nukleinovykh kislotakh. XI. Vzaimosviaz' mezhdu kineticheskimi parametrami khimicheskogo ligirovaniia v modifitsirovannykh DNK-dupleksakh i strukturoi reaktsionnogo uzla.

To characterize structural factors affecting kinetic parameters of chemical ligation, DNA duplexes with various arrangements of reacting groups in the ligation site have been synthesized and studied. The modifications included replacement of a deoxythymidine with a uridine or a nucleoside having reversed configuration at C2' and/or C3' atoms, the modified residue being phosphate donor or acceptor; introduction of an "extra" nucleotide residue; replacement of a G.C pair second to the junction with a noncomplementary G.G pair. Thermal stability of the anomalous nucleotide duplexes has been characterized. Based on analysis of the kinetic parameters of chemical ligation, a suggestion is made about the conformation of the reactive site.

[T4-DNA ligase: substrate properties of synthetic DNA-duplexes with structural anomalies]. / T4-DNK-ligaza: substratnye svoistva sinteticheskikh DNK-dupleksov so strukturnymi anomaliiami.

Structural defects, affecting T4 DNA ligase function, were revealed with the help of synthetic DNA duplexes, containing modifications at single nick. Changes of configuration at C2' and C3' atoms of furanose in the acceptor terminus lead to total blocking of the nick sealing activity of T4 DNA ligase. On the contrary, substitution of 3'-terminal deoxyribonucleotide for ribonucleotide doesn't affect the enzyme's action. The duplex looses all of it's substrate activity if the next from the nick G.C pair is substituted for the noncomplementary G.C pair. In DNA duplexes containing an unpaired base in the nick, elimination of the extrahelical nucleotide proceeds the ligation step. In these cases the duplex substrate activity decreases depending on the extent of extrahelical base stacking into the double stranded DNA.

[DNA-like duplexes containing repetitive sequences. VII. Chemico-enzymatic synthesis of polymers with fragments of natural promotors]. / DNK-podobnye dupleksy, soderzhashchie povtory. VII. Khimiko-fermentativnyi sintez polimerov s fragmentami prirodnykh promotorov.

Two types of DNA-duplexes containing the repeating fragments of natural promoters have been obtained starting from synthetic oligodeoxyribonucleotides TGCATTATAA, AACTAGTT, AGTTAACT. Deca- and octanucleotides have been synthesized by solid phase method with stepwise or blockwise chain elongation. UV- and CD-spectroscopy has been used to study the physico-chemical properties of the synthetic oligonucleotides. Polycondensation of oligonucleotides induced by water-soluble carbodiimide (chemical ligation) or T4-polynucleotide ligase allowed to synthesize the promoter models. The degree of polymerization varied from 2 to 8 in case of chemical ligation and from 2 to 30 in case of enzymatic ligation. A new chain length regulation technique has been developed by means of addition of a terminator of polycondensation (unphosphorylated oligonucleotide) in the reaction mixture.