Chance and Necessity in the Evolution of Matter to Life: A Comprehensive Hypothesis

Specialists in several branches of life sciences are trying to solve, piece by piece, the immensely complex puzzle of the origin of life. Some parts of the puzzle seem to appear with a rather high degree of clarity, while others remain totally obscure. We cannot be sure that life emerged only on our Earth, but we believe that the presence of large amounts of water in its liquid state is absolutely essential for the emergence and evolution of living matter. We can also assume that the latter exploits everywhere the same light elements, mainly C, H, O, N, S, and P, and somehow manipulates the same simple monomeric and polymeric organic compounds, such as alpha-amino acids, carbohydrates, nucleic bases, and surface-active carboxylic acids. The author contributes to the field by stating that all fundamental particles of our matter are “homochiral” and predominantly produce in an absolute asymmetric synthesis amino acids of L-configuration and carbohydrates of D-series. Another important point is that free atmospheric oxygen mainly stems from the photolysis of water molecules by cosmic irradiation and is not necessarily bound to living organisms on the planet.

PROSPECTS FOR CREATING RADON CONTAINING AGENTS IN RADIONUCLIDE THERAPY

One of the methods for treating oncological diseases is application of short-lived radionuclides. Existing risks of intoxication and radioactive contamination can be eliminated by introduction of a short-lived radon isotope into a hard strong fullerene coat. To increase the effectiveness of these drugs it is promising to introduce structural fragments of amino acids, peptides, steroid hormones, nucleic bases or heterocyclic compounds being able to accumulate exactly in tumoral but not in healthy tissues of the body. The article presents data on quantum-chemical simulation of electronic structure and thermodynamic stability of fullerenol radon-containing agents of radionuclide therapy on the example of a model cortisonefullerenol bioconjugate.

A Fluorescent Assay to Search for Inhibitors of HIV-1 Integrase Interactions with Human Ku70 Protein, and Its Application for Characterization of Oligonucleotide Inhibitors

The search for compounds that can inhibit the interaction of certain viral proteins with their cellular partners is a promising trend in the development of antiviral drugs. We have previously shown that binding of HIV-1 integrase with human Ku70 protein is essential for viral replication. Here, we present a novel, cheap, and fast assay to search for inhibitors of these proteins’ binding based on the usage of genetically encoded fluorescent tags linked to both integrase and Ku70. Using this approach, we have elucidated structure-activity relationships for a set of oligonucleotide conjugates with eosin and shown that their inhibitory activity is primarily achieved through interactions between the conjugate nucleic bases and integrase. Molecular modeling of HIV-1 integrase in complex with the conjugates suggests that they can shield E212/L213 residues in integrase, which are crucial for its efficient binding to Ku70, in a length-dependent manner. Using the developed system, we have found the 11-mer phosphorothioate bearing 3’-end eosin-Y to be the most efficient inhibitor among the tested conjugates.

Interactions of Thymine and Uracil with Copper, Cobalt and Silver Ferrocyanides and the Implications in Chemical Evolution

Effects on pH based adsorption of nucleic acid bases (thymine and uracil) at two different concentrations 1 x 10-4 M and 1 x 10-5 M on copper, cobalt and silver ferrocyanides were studied over a pH range (1.0 – 10.0) at temperature 30±1ºC. The progress of adsorption was followed spectrophotometrically by measuring the UV absorbance of the nucleic acid base solutions at their corresponding max. Maximum adsorptions were found at neutral pH for both thymine and uracil. Effects of concentrations on adsorption of thymine and uracil on copper, cobalt and silver ferrocyanides were studied in a concentration range 10-4 – 10-5 M at neutral pH 7.0 ± 0.1 and at temperature 30±1°C. The interaction followed the Langmuir type of adsorption in general in the concentration range of 10-4 to 10-5 M of thymine and uracil solution. The uptake of nucleic bases on metal ferrocyanides followed the order of CuFc > AgFc > CoFc for the adsorption of thymine and CuFc > CoFc > AgFc for the adsorption of uracil. Effects of the presence of salts on the adsorption of thymine and uracil on metal ferrocyanides also had been studied. The insoluble metal ferrocyanides’ interaction with biomolecules must have either formed metal complexes or could have enhanced the formation of biopolymers in fluctuating environment.

Convenient and Efficient Syntheses of Peptide Nucleic Acid Purine Monomers

Currently, peptide nucleic acids (PNAs) play an important role as therapeutic agents, molecular tools for diagnosis and detection of genetic diseases as well as in biosensor probes. This research aims to optimize the synthesis of aeg- and γ-(S)-Me PNA monomers based on L-Ala, intended for oligomerization according to the Boc protocol. The monomers were obtained through the condensation of the corresponding pseudopeptides with carboxymethyl purine nucleic bases. During the work, the optimization of benzyloxycarbonyl- N6-adenine-9-yl-acetic acid and benzyloxycarbonyl-N2-guanine-9-ylacetic acid was carried out. The synthesis of benzyloxycarbonyl-N6-adenine-9-yl-acetic acid was conducted in three stages based on adenine with an overall yield of 22%. At the same time, the conditions for effective recrystallization of the mixture after alkylation of benzyloxycarbonyl-N6-adenine with ethyl bromoacetic acid ether have been developed to isolate the desired N9-regioisomer. Also, the optimization of a known method for producing benzyloxycarbonyl-N2-guanine-9-ylacetic acid from 2-amino-6-chloropurine was carried out. The total yield of the five-stage scheme was 55%. Condensation of aeg- and γ-(S)-Me pseudopeptides with benzyloxycarbonyl-N6-adenine-9-yl-acetic acid and benzyloxycarbonyl-N2-guanine-9-yl-acetic acid was performed by the standard carbodiimide method, DCC/HOBt in DMF followed by the removal of C-terminal methyl protective group by alkaline hydrolysis. The structure of the new compounds obtained was confirmed by spectral analysis methods. This work provides simple and optimized methods for obtaining protected carboxymethyl purine bases and increasing the efficiency of the synthesis and synthesized purine PNA monomers in an acceptable yield.

The Possibility of Blocking the Process of DNA Base Pairs Opening by Hydrogen Peroxide

One of the most progressive methods of cancer treatment is the ion beam therapy. Simulations of the water radiolysis show that the most long-living species in the cell medium are hydrogen peroxide (H2O2) molecules. But up to the present time, the role of H2O2 molecules in the deactivation of cancer cells has not been determined yet. To understand the possible role of H2O2 in the ion beam therapy, the competitive interaction of H2O and H2O2 molecules with nucleic bases in a pair on the different stages of genetic information transfer is studied in the present work. The method of atom-atomic potential functions is used in the calculations. It is shown that some configurations of A·T, and G·C complementary pairs are stabilized muchbetter by an H2O2 molecule as compared to a water molecule. The formation of such interaction complexes can terminate the processes of DNA unzipping by enzymes and consequently block the genetic information transfer processes in cancer cells during the ion beam treatment. An experimental method of verification of the interaction of hydrogen peroxide with nucleic base pairs is proposed.