Base pairing-induced shift in tautomeric equilibrium of a promutagenic analogue, N6-methoxyadenosine

AbstractThe nuclear magnetic resonance spectra of N6-methoxyadenosine and of uridine, both methylated in the 2′-,3′- and 5′-positions to obtain solution in deuterochloroform, reveal the formation of hetero-associates in which the amino—tautomeric equilibrium is shifted to the amino form. These results ar discussed in terms of the mutagenicity of O-methylhydroxylamine which converts adenosine to N6-methoxyadenosine

Effects of Portland cement addition on Young’s modulus of geopolymer concrete cured at ambient conditions

This paper presents the results of Young’s modulus and Poisson’s ratio tests conducted on samples made of low-calcium fly ash-based geopolymer concrete samples and on samples with a 10% addition of Portland cement, cured at ambient conditions. Furthermore, the measurement system, as well as sampling and sample preparation methodology, are discussed. Strain was tested concurrently using resistive strain gauges and extensometer on cylinder-shaped samples with a diameter of 150 mm and height of 300 mm. Keywords: engineering, construction materials, geopolymer concrete, Young’s modulus, Poisson’s ratio, alkali-activated concret

Thermodynamics of specific protein-RNA interactions.

Description of the recognition specificity between proteins and nucleic acids at the level of molecular interactions is one of the most challenging tasks in biophysics. It is key to understanding the course and control of gene expression and to the application of the thus acquired knowledge in chemotherapy. This review presents experimental results of thermodynamic studies and a discussion of the role of thermodynamics in formation and stability of functional protein-RNA complexes, with a special attention to the interactions involving mRNA 5' cap and cap-binding proteins in the initiation of protein biosynthesis in the eukaryotic cell. A theoretical framework for analysis of the thermodynamic parameters of protein-nucleic acid association is also briefly surveyed. Overshadowed by more spectacular achievements in structural studies, the thermodynamic investigations are of equal importance for full comprehension of biopolymers' activity in a quantitative way. In this regard, thermodynamics gives a direct insight into the energetic and entropic characteristics of complex macromolecular systems in their natural environment, aqueous solution, and thus complements the structural view derived from X-ray crystallography and multidimensional NMR. Further development of the thermodynamic approach toward interpretation of recognition and binding specificity in terms of molecular biophysics requires more profound contribution from statistical mechanics

Stereospecific synthesis by the sodium salt glycosylation method of halogeno benzimidazole 2'-deoxyribose analogues of the inhibitor of hnRNA synthesis, 5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB)

The recently developed stereospecific sodium salt glycosylation procedure has been successfully applied to the synthesis of the β-ᴅ-2′-deoxyribofuranosides of benzimidazole, 5,6-dihalogeno benzimidazoles, and some 2-substituted analogues in high yield. The 5,6-dibromo analogue was obtained by bromination of the parent nucleoside. These have all been characterized by spectro­scopic methods, including 1H NMR, which permitted analyses of their solution conformations and comparison with those of the corresponding ribofuranosides. Some biological aspects, including preliminary results on cytotoxicity and antiviral activity, are briefly considered

Dynamical insight into Caenorhabditis elegans eIF4E recognition specificity for mono-and trimethylated structures of mRNA 5′ cap

Abstract Specific recognition and binding of the ribonucleic acid 5′ termini (mRNA 5′ cap) by the eukaryotic translation initiation factor 4E (eIF4E) is a key, rate limiting step in translation initiation. Contrary to mammalian and yeast eIF4Es that discriminate in favor of 7-methylguanosine cap, three out of five eIF4E isoforms from the nematode Caenorhabditis elegans as well as eIF4Es from the parasites Schistosome mansoni and Ascaris suum, exhibit dual binding specificity for both 7-methylguanosine-and N2,N2,7-trimethylguanosine cap. To address the problem of the differences in the mechanism of the cap recognition by those highly homologic proteins, we carried out molecular dynamics simulations in water of three factors, IFE-3 and IFE-5 isoforms from C. elegans and murine eIF4E, in the apo form as well as in the complexes with 7-methyl-GDP and N2, N2,7-trimethyl-GDP. The results clearly pointed to a dynamical mechanism of discrimination between each type of the cap, viz. differences in mobility of the loops located at the entrance into the protein binding pockets during the cap association and dissociation. Additionally, our data showed that the hydrogen bond involving the N2-amino group of 7-methylguanosine and the carboxylate of glutamic acid was not stable. The dynamic mechanism proposed here differs from a typical, static one in that the differences in the protein-ligand binding specificity cannot be ascribed to formation and/or disruption of well defined stabilizing contacts