Modelling the radioactive contamination of commercial fish species in the Barents Sea following a hypothetical short-term release to the Stepovogo Bay of Novaya Zemlya.

A dynamic modelling of radionuclides accumulation in commercial species in the Barents Sea is performed for hypothetical SCR accident with the dumped submarine K-27 at the Stepovogo Bay. Box radioecological model is employed for calculating the radionuclides dynamics in water, bottom sediments and marine biota. The model takes into account the seasonal fish migrations in the Barents Sea. The model allows predicting the dynamic effects of the radionuclide transfer in fish in case of an accidental water contamination. Maximum 137Cs activity concentrations in bottom sediments from the eastern part of the Barents Sea could be reached as late as 5-6 years after the accidental release. Based on the results of model calculations, assessment was made of doses to humans from consumption of seafood contaminated after a hypothetical SCR accident with K-27 at the Stepovogo Bay. The peak activity concentration of the released 137Cs in fish from the Stepovogo Bay is calculated to be 109 Bq∙kg-1, 90Sr - 12 Bq∙kg-1; both estimates are below the permissible activity concentrations of these radionuclides in commercial fish. Predicted maximum annual dose from consumption of fish from the Stepovogo Bay is 47 ± 18 µSv∙year-1, the Barents Sea fish - less than 3∙10-6 µSv∙year-1.137Cs is the major dose contributor; it provides more than 99% to the annual dose Radiation risks from consumption of the Barents Sea commercial fish are evaluated to be negligible in case of a hypothetical SCR accident with the submerged submarine K-27 in Stepovogo Bay of Novaya Zemlya.

Synthesis of polyacrylamides N-substituted with PNA-like oligonucleotide mimics for molecular diagnostic applications.

Two types of oligonucleotide mimics relative to peptide nucleic acids (PNAs) were tested as probes in nucleic acid hybridisation assays based on polyacrylamide technology. One type of mimic oligomers represented a chimera constructed of PNA and phosphono-PNA (pPNA) monomers, and the other one contained pPNA residues alternating with PNA-like monomers on the base of trans -4-hydroxy-L-proline (HypNA). A chemistry providing efficient and specific covalent attachment of these DNA mimics to acrylamide polymers using a convenient approach based on the co-polymerisation of acrylamide and some reactive acrylic acid derivatives with oligomers bearing 5'- or 3'-terminal acrylamide groups has been developed. A comparative study of polyacrylamide conjugates with oligonucleotides and mimic oligomers demonstrated the suitability and high potential of PNA-pPNA and HypNA-pPNA chimeras as sequence-specific probes in capture and detection of target nucleic acid fragments to serve current forms of DNA arrays.

Convenient approaches to the synthesis of oligonucleotide macrocycles containing non-nucleotide linkers.

Two convenient, practical routes to the synthesis of non-nucleotide bridged cyclic oligonucleotides have been developed. The first procedure included circularization of oligonucleotides by template-directed ligation on solid phase, while the second procedure involved preparation of a circular oligomer by non-template chemical ligation of a linear precursor in solution. Using these approaches, a series of single- and double-stranded cyclic oligonucleotides with non-nucleotide bridges has been synthesized.

Synthesis and evaluation of some properties of chimeric oligomers containing PNA and phosphono-PNA residues.

In an attempt to improve physico-chemical and biological properties of peptide nucleic acids (PNAs), particularly water solubility and cellular uptake, the synthesis of chimeric oligomers consisted of PNA and phosphono-PNA analogues (pPNAs) bearing the four natural nucleobases has been accomplished. To produce these chimeras, pPNA monomers of two types containing N-(2-hydroxyethyl)phosphonoglycine, or N-(2-aminoethyl)phosphonoglycine backbone, were used in conjunction with PNA monomers representing derivatives of N-(2-aminoethyl)glycine, or N-(2-hydroxyethyl)glycine. The oligomers obtained were composed of either PNA and pPNA stretches or alternating PNA and pPNA monomers. The examination of hybridization properties of PNA-pPNA chimeras to DNA and RNA complementary strands in comparison with pure PNAs, and pPNAs as well as DNA-pPNA hybrids and DNA fragments confirmed that these chimeras form stable complexes with complementary DNA and RNA fragments. They were found to be resistant to degradation by nucleases. All these properties together with good solubility in water make PNA-pPNA hybrids promising for further evaluation as potential therapeutic agents.

Synthesis of DNA analogues with novel carboxamidomethyl phosphonamide and glycinamide internucleoside linkages.

Thymidine oligonucleotide analogues with phosphodiester bonds fully substituted by carboxamidomethyl phosphonamide, or glycinamide linkages were synthesized on a solid support, and their hybridization properties toward DNA and RNA targets were determined by Tm analysis.

Modern phosphotriester synthesis of long oligonucleotides and their use in genetic engineering.

Long oligodeoxyribonucleotides synthesized by the modern phosphotriester method, which is based on the use of O-nucleophilic intramolecular catalysis, were applied for the construction of artificial DNAs and directed mutagenesis of some genes.

Application of new catalytic phosphate protecting groups for the highly efficient phosphotriester oligonucleotide synthesis.

An effective procedure for the synthesis of oligonucleotides by the phosphotriester method has been developed. The procedure is based on the use of phosphate protecting groups enabling O-nucleophilic intramolecular catalysis in the reaction of internucleotide bond formation under the action of arylsulfonyl chlorides and their derivatives. Using this new procedure, the time needed to perform one elongation step on polymer support is 7-8 min. The effectiveness of the methodology has been demonstrated in the synthesis of many oligodeoxyribonucleotides of different length with high yields.

Rapid synthesis of long-chain deoxyribooligonucleotides by the N-methylimidazolide phosphotriester method.

A modified phosphotriester method has been employed for the efficient chemical synthesis of long-chain deoxyribooligonucleotides. During the course of this work, a general and rapid procedure was developed for the preparation of 24-62-mers in solution. Preparative reversed phase column chromatography on silanized silica gel was used to purify triester intermediates starting from 10-mers. The rapid synthesis of 32-mer and 42-mer on glass and silica gel supports using suitably protected 2-8-mer blocks as coupling units has been also accomplished. In particular, a convenient procedure for the solid-phase synthesis of oligonucleotide blocks bearing 3'-terminal phosphodiester groups is described.