Site-specific modification of the 5"-terminal fragment of PGY1/MDR1 gene mRNA by reactive conjugates of antisense oligonucleotides

The site-specific modification of the 5"-terminal fragment of PGY1/MDR1 mRNA by oligodeoxyribonucleotide conjugates bearing residues of bleomycin A₅ (Blm), cobalt(ii) tetracarboxyphthalocyanine (Phcn), 4-[N-(2-chloroethyl)-N-methylamino]benzylamine (RCl), or perfluoroarylazide (Az) was studied. Conjugates of oligonucleotides complementary to the RNA sequences 123—138 and 155—166 selectively modify RNA in the vicinity of these regions. The highest efficacy (up to 50%) was achieved in reactions with alkylating and perfluoroarylazide conjugates of oligonucleotides. Conjugates of perfluoroarylazide with 2"-O-modified oligonucleotides are much more efficient than analogous conjugates with oligodeoxyribonucleotides (extents of RNA modification are 40—50% and 20%, respectively).     

Magnetooptical bistability of a layered semiconductor in the region of exciton absorption

The effect of weak external magnetic fields on the conditions for implementing optical bistability in the region of exciton absorption of layered semiconductors has been theoretically investigated. By the example of the 2H polytype of lead diiodide, it is shown that, changing the strength of an external magnetic field, one can form conditions for implementing bistability and effectively control the position and sizes of the hysteresis loop of exciton absorption.     

The estimation of the degree of coherence of mutually orthogonal beams: New approaches

A theoretical model for calculating the motion dynamics of the particles of different light-scattering mechanisms in the energy inhomogeneous optical field is suggested. The direct relationship between the motion velocity of the tested particles in the created field and the degree of coherence of mutually orthogonal linearly polarized plane waves is demonstrated.     

Suppression of MDR1 gene expression by chemically modified siRNAs

The ability of chemically modified siRNAs targeted to MDR1 mRNA to inhibit P-glycoprotein expression and to restore sensitivity of cancer cells to antibiotic vinblastine was investigated. The effects of chemical modifications on RNA stability in cell culture medium and inhibition of MDR1 gene expression were tested. We found that siRNAs containing 2′-O-methyl ribonucleotides within either sense or/and antisense strands display high stability in serum but exhibit a significant reduction in the biological activity. The protection of 3′-ends of siRNA by introduction of 3′-3′-inverted phosphodiester bonds and two 2′-O-methyl ribonucleotides in protruding 3′-ends considerably increase their biological activity, which allows a 30-fold decrease in the cytostatic agent concentration required for cancer cell death. The data obtained demonstrate that the chemically modified siRNAs can be considered as potential therapeutics, which enhances the efficiency of cancer chemotherapy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1227–1235, July, 2006.     

Artificial ribonucleases 6. Ribonuclease activity of tetrapeptides based on amino acids involved in the catalytic site of RNase T1

Tetrapeptides based on amino acids involved in the catalytic site of RNase T1 were synthesized. These peptides interact with a 96-mer fragment of HIV-1 RNA, which results in phosphodiester bonds splitting. The efficacy of RNA cleavage depends on the mutual arrangement of oppositely charged amino acids (Glu and Arg or Lys) in a peptide. The introduction of an additional cationic fragment (based on bis-quaternary salts of 1,4-diazabicyclooctane) into an RNase mimetic leads to a considerable increase in the efficiency of RNA depolymerization. For Part 5, see Ref. 1. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2596–2604, November, 2005.     

Artificial ribonucleases. 5. Synthesis and ribonuclease activity of tripeptides composed of amino acids involved in catalytic centers of natural ribonucleases

The characteristic features of the spatial arrangement of the main functional groups involved in catalytic centers of ribonucleases and nucleases were revealed by computer analysis of the catalytic centers of these enzymes. Based on the results of computer simulation, tripeptides containing Lys, Arg, His or Hia, Thr, and Asn in different combinations were synthesized. In these tripeptides, the distances between the corresponding functional groups are equal to those observed in natural enzymes. The efficacy of RNA cleavage with Arg- and His-containing tripeptides depends on their structure and correlates with the overall positive charge of these compounds. Of all the tripeptides under consideration, compounds bearing the overall charge of +4 exhibit the highest ribonuclease activity.     

Metrology of degree of coherence of circularly polarized optical waves

The use of the method of field polarization modulation for defining the degree of coherence of circularly polarized waves is offered. The role of the reference circularly polarized wave in transforming the spatial distribution of polarization into the depth of visibility modulation of the resulting distribution, which can be metrologically estimated and analyzed, is demonstrated.     

Magnetooptical absorption of a molecular crystal in the exciton frequency range

Nonlinear absorption of a molecular crystal in an external magnetic field is considered. The exciton absorption shape functions under polarized laser radiation and a weak magnetic field, as well as the mechanisms responsible for the formation of a hysteresis loop in the dependence of the output light intensity on the applied magnetic field, were studied for the particular case of benzene. It was established that, for the magnetooptical response of the molecular crystal under study, the formation of bistable loops is inverse in character, which makes it possible to monitor and control the behavior of bistable elements in optical logics systems with an external magnetic field at a fixed illumination frequency.     

Nonlinear magnetooptical absorption in a semiconductor

The influence of an external magnetic field on the optical characteristics of the exciton spectra of a semiconductor is studied. It is shown that the diamagnetic shift of the exciton level essentially changes the dynamics of the exciton absorption. The combination of the excitonic and magnetic properties of a crystal in the range of excitonic frequencies gives new opportunities to control the bistable behavior of the crystal. It is revealed that the magnetooptical response of the semiconductor to the laser field gives rise to bistable loops with respect to both the intensity of the incident light and the magnitude of the magnetic field.