Efficient conjugation and preferential DNA binding of oligonucleotides containing 2′-O-(2-oxoethyl)arabinouridine

Oligodeoxyribonucleotides were synthesized that contain a novel nucleoside, 2′-O-(2-oxoethyl)arabinouridine. Whereas such oligonucleotides showed only a slight reduction in the T_M values of their complexes with complementary DNA, a significant destabilization was observed in the case of duplexes formed with RNA. This may be explained by the C_2′-endo conformation of 2′-O-(2,3-dihydroxypropyl)arabinouridine as demonstrated by NMR experiments in D₂O. The modified oligonucleotides were used to synthesize a number of conjugates with dyes, biotin and a N-modified laminin peptide, by hydrazone and oxime formation. We suggest that the 2′-arabinoaldehyde-containing DNA duplexes may be valuable tools for affinity modification of DNA-binding proteins.     

Total stepwise solid-phase synthesis of oligonucleotide-(3'-->N)-peptide conjugates

[structure: see text] An efficient total stepwise solid-phase synthesis of oligonucleotide-(3'-->N)-peptide conjugates is described that makes use of either a controlled pore glass support or macroporous polystyrene beads. Extending our previous homoserine linker approach, we prepared a range of conjugates containing one of four different cell or nuclear penetration peptides together with oligonucleotides containing 2'-deoxynucleoside or 2'-O-methylribonucleoside phosphodiesters, or gapmers containing 2'-deoxyphosphorothioates. The route also allows incorporation of a fluorescent label within the conjugate for cell uptake studies.     

Efficient conjugation of peptides to oligonucleotides by "native ligation"

A new strategy has been developed for conjugation of peptides to oligonucleotides. The method is based on the "native ligation" of an N-terminal thioester-functionalized peptide to a 5'-cysteinyl oligonucleotide. Two new reagents were synthesized for use in solid-phase peptide and oligonucleotide synthesis, respectively. Pentafluorophenyl S-benzylthiosuccinate was used in the final coupling step in standard Fmoc-based solid-phase peptide assembly. Deprotection with trifluoracetic acid generated in solution peptides substituted with an N-terminal S-benzylthiosuccinyl moiety. O-trans-4-(N-alpha-Fmoc-S-tert-butylsulfenyl-L-cysteinyl)aminoc yclohe xyl O-2-cyanoethyl-N,N-diisopropylphosphoramidite was used in the final coupling step in standard phosphoramidite solid-phase oligonucleotide assembly. Deprotection with aqueous ammonia solution generated in solution 5'-S-tert-butylsulfenyl-L-cysteinyl functionalized oligonucleotides. Functionalized peptides and oligonucleotides were used without purification in native ligation conjugation reactions in aqueous/organic solution using tris-(2-carboxyethyl)phosphine to remove the tert-butylsulfenyl group in situ and thiophenol as a conjugation enhancer. A range of peptide-oligonucleotide conjugates were prepared by this route and purified by reversed-phase HPLC.     

Analysis of the results of calibrating meteoritic olivine crystals with238U nuclei at the Bevalac accelerator

The results are presented of calibrating the sensitivity of olivine crystals from meteorites by the²³⁸U nuclei produced at the Bevalac accelerator. The comparative studies of the spectra of the etchable track lengths due to the²³⁸U nuclei and to fossil tracks in these olivines have shown that the group of the 210 m fossil tracks observed in 1980 at the LNR, JINR is due to the galactic cosmic-ray nuclei of the Th-U group. As regards the origin of the 340–360 m group of fossil tracks which were considered in [2] to be candidates for superheavy nuclei in cosmic rays the presence of the track with a length of up to 360 m in the calibrating²³⁸U track length spectra indicates that the above interpretation has to be questioned. The possible ways of the unambiguous identification of the group of the abnormally long fossil tracks are discussed.In conclusion the authors express their deep gratitude to Academician G.N. Flerov for thoughtful guidance and permanent attention to this study. The authors wish to thank Dr. G.M. Ter-Akopian for very useful discussions and advice and also for his help during the calibrations on Bevalac, Dr. R.I. Petrova for her help in preparing olivine crystal mounts and for their subsequent annealing and etching, and Mrs. G.G. Bankova and G.P. Knyazeva for the thorough microscopic measurements of the²³⁸U track spectra.     

Specific features of magnetic properties of three-component magnetic superlattices based on Fe/Co/Mo

Synthesis of three-component magnetic superlattices based on the Fe/Co/Mo system by cathode sputtering in an electron-oscillating discharge and their complex investigations have been performed for the first time. The fields have been investigated by X-ray diffraction, vibrational magnetometry, and Mössbauer spectroscopy with the use of completely computerized systems. Oscillations of the main magnetic parameters with a change in the Mo thickness and giant spontaneous magnetization have been found. The properties of three-component superlattices are compared with those of the analogous system based on Fe/Mo.     

Transmutation of 129I, 237Np, 238Pu, 239Pu, and 241Am using neutrons produced in target-blanket system ‘Energy plus Transmutation’ by relativistic protons

Target-blanket facility ‘Energy + Transmutation’ was irradiated by proton beam extracted from the Nuclotron Accelerator in Laboratory of High Energies of Joint Institute for Nuclear Research in Dubna, Russia. Neutrons generated by the spallation reactions of 0.7, 1.0, 1.5 and 2 GeV protons and lead target interact with subcritical uranium blanket. In the neutron field outside the blanket, radioactive iodine, neptunium, plutonium and americium samples were irradiated and transmutation reaction yields (residual nuclei production yields) have been determined using γ-spectroscopy. Neutron field's energy distribution has also been studied using a set of threshold detectors. Results of transmutation studies of ¹²⁹I, ²³⁷Np, ²³⁸Pu, ²³⁹Pu and ²⁴¹Am are presented.      

Characteristics of a cylindrical magnetron and reactive sputtering of binary compound films

The characteristics of a cylindrical magnetron, such as the dependences of the discharge voltage, chamber pressure, and plasma radiation intensity on the reactive gas flow rate and discharge current, are studied. In this magnetron, titanium nitride (TiN) and titanium dioxide (TiO₂) films are obtained by reactive magnetron sputtering. The transmission and reflection spectra of the films in the visual range are taken. From the transmission data for the TiO₂ films, their refractive index and absorption factor in the wavelength range 350–800 nm, as well as the porosity, are found by the Valeev method. The variation of the fundamental absorption edge with film thickness is determined with the Urbach formula.     

Synthesis of oligo-2′-<Emphasis Type="Italic">O</Emphasis>-methylribonucleotides containing α-amino acid residues in 2′-position

Oligo-2′-O-methylribonucleotides containing residues of phenylalanine, histidine, and lysine amides were synthesized with the use of new phosphoramidites of 2′-aminoacid derivatives of uridine. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 775–783, April, 2007.