Is FapyG Mutagenic?: Evidence from the DFT Study

2,6‐diamino‐4‐oxo‐5‐formamidopyrimidine (FapyG) is an oxidatively damaged product of guanine (G), which is mainly formed through metabolic processes that produce OH radicals. It has been proposed that in bacterial cells, FapyG retains the coding properties of G, and is, therefore, not mutagenic. However, in mammalian cells, FapyG induces G to thymine (T) mutation more dominantly than another ubiquitous oxidative lesion, that is, 8‐oxoguanine (8‐oxoG). The exact reasons for these coding properties of FapyG are not properly understood. In order to rationalize the cause of FapyG‐mediated mutagenesis, all of the possible base‐pair interactions of FapyG with cytosine (C), adenine (A), and T, in both anti‐ and syn‐ conformations, are studied in detail by using density functional theory (DFT). The effects of solvation on the coding properties of FapyG are also evaluated. We demonstrate that the anti‐FapyG:C base pair has the highest binding energy, and that the base‐pair alignment is similar to that of the normal G:C base pair. Therefore, insertion of C opposite anti‐FapyG is preferred over the other DNA bases. This could be the reason for the non‐mutagenic behavior of FapyG in bacterial cells. However, as the binding patterns and energies of anti‐FpyG:A and syn‐FapyG:A base pairs are similar, and these are also similar to those of the T:A base pair, mammalian polymerases may not distinguish between FapyG and T. As a result, A would be mistakenly inserted opposite either anti‐FapyG or syn‐FapyG, resulting in G to T transverse mutation.     

An Efficient Synthesis and Antimicrobial Studies of Bioactive 4H-1,4-Benzothiazine and Their Sulfone Derivatives

Abstract

4H-1,4-benzothiazines were prepared by condensation followed by oxidative cyclization of substituted 2-aminobenzenethiols with β-diketones in dimethylsulfoxide. On refluxing with 30% hydrogen peroxide in glacial acetic acid, 4H-1,4-benzothiazines yielded 4H-1,4-benzothiazine-1,1-dioxides. Structural evaluation has been done by spectral and elemental analysis. All the synthesized compounds were evaluated for their antibacterial and antifungal activity and all these have shown moderate to high activity against the test microbes.

Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures and tables.     

Synthesis, conformational analysis and biological studies of cyclic cationic antimicrobial peptides containing sugar amino acids

Sugar amino acid based 24-membered macrocyclic C2-symmetric cationic peptides were designed and synthesized. The cationic group was introduced in the sugar amino acids. The conformation of these cyclic compounds was ascertained through NMR techniques, which proved they were amphipathic in nature. All the compounds were bacteriolytic, showed good activity against the Gr(+ve) and Gr(-ve) bacteria, and exhibited low hemolytic activity.     

Spectroscopic investigations of nanohydroxyapatite powders synthesized by conventional and ultrasonic coupled sol-gel routes

In the present work, the synthesis and characterization of nano-HAP powders by a novel ultrasonic coupled sol-gel synthesis is reported. The obtained powders were sintered by conventional means at different temperatures. In addition to this, HAP powders prepared through the sol-gel method without the aid of the ultrasonic waves is also studied. The obtained nano-HAP powders were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscopic (SEM) techniques. The results have proved that the nano-HAP powders synthesized by ultrasonic coupled sol-gel synthesis showed remarkable reduction in the particle size when compared with the conventional sol-gel method and hence these powders could be used as a coating material in biomedical applications.     

Synthesis of 2-deoxy-2-c-alkyl glycal and glycopyranosides from 2-hydroxy glycal ester

A method to convert 2-hydroxy glycal ester to the corresponding 2-deoxy-2-C-alkyl glycal in a facile manner, through key reactions including (i) C-allylation at C-1, (ii) Wittig reaction, and (iii) Cope rearrangement of a 1,5-diene derivative, is reported. The α-anomer of the 1,5-diene derivative underwent Cope rearrangement to afford 2-deoxy-2-C-glycal derivative, whereas the β-anomer was found to be unreactive. Employing this sequence, 3,4,6-tri-O-benzyl-2-O-acetyl-1,5-anhydro-d-arabino-hex-1-enitol was transformed to 3,4,6-tri-O-benzyl-2-deoxy-2-C-alkyl-1,5-anhydro-D-arabino-hex-1-enitol. 2-Deoxy-2-C-alkyl glycal derivative is a suitable glycosyl donor to prepare 2-deoxy-2-C-alkyl glycosides, mediated through haloglycosylation and a subsequent dehalogenation. A number of 2-deoxy-2-C-alkyl glycosides, with both glycosyl and nonglycosyl moieties at the reducing end, are thus prepared from the glycal.     

Dense-medium modifications to jet-induced hadron pair distributions in Au+Au collisions at sqrt s NN=200 GeV

Azimuthal correlations of jet-induced high-p(T) charged hadron pairs are studied at midrapidity in Au+Au collisions at sqrt[s(NN)]=200 GeV. The distribution of jet-associated partner hadrons (1.0相似文献   

Effect of In ions doping on the structural and magnetic properties of Mg0.2Mn0.5Ni0.3InxFe2−xO4 spinel ferrites

Effect of substitution of diamagnetic trivalent indium ions on the composition Mg_0.2Mn_0.5Ni_0.3In_xFe_2−xO₄ with x varying from 0.1 to 0.3 in steps of 0.1 using citrate precursor techniques has been investigated. Single-phase cubic spinel structure of these samples has been confirmed from X-ray diffraction analyses. Micro structural features were examined by TEM images. Lattice constant ‘a’ initially increases up to x = 0.1 and thereafter it decreases with further increase in x. This indicates that variation of ‘a’ with x do not obey Vegard's law. Nonlinear behavior of ‘a’ with x may be due to substitutional effect of larger In³⁺ ions (0.91Å) with smaller Fe³⁺ ions (0.67Å) in Mg-Mn-Ni ferrite. Ferrites have been investigated for their structural and magnetic properties such as variations in lattice constant, saturation magnetization, coercivity, retentivity, initial permeability, magnetic loss and relative loss factor (RLF). Fairly constant value of initial permeability over a wide frequency range (0.075–10 MHz) and low values of relative loss factor of order of 10⁻⁶–10⁻⁵ in same frequency range are main achievement of present investigations. RLF has been reduced by three orders of magnitude as compared to those samples prepared by conventional method. Low values of relative loss factor even at a high frequency indicate that prepared materials may have great potential for use in microwave devices. Possible mechanisms contributing to these properties have been discussed in this paper.     

Searching critical-point nuclei in Te- and Xe-isotopic chains using sextic oscillator potential

We have identified the nuclei in the Te- and Xe-isotopic chains lying close to the critical point, through which the shape phase transition occurs, by using the sextic oscillator potential formalism. It has been found that ¹¹⁰Te, ¹²⁴Te, and ¹²⁴Xe isotopes are the most promising candidates for the critical-point nuclei slightly above the Z = 50 proton shell closure.     

Synthesis and antibacterial evaluation of nitrogen containing novel heterocyclic chalcones

Thirteen different novel heterocyclic chalcones were synthesized using cycloaddition and Claisen–Schmidt condensation reactions. These newly synthesized compounds were characterized by their spectral studies and structure of (E)-3-(4-methoxyphenyl)-1-(5-methyl-1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)prop-2-en-1-one (4h) was also evidenced by single crystal X-ray studies. These compounds were evaluated for antibacterial activities against seven bacterial strains in vitro. Compounds 4b and 4c containing 4-fluoro and 4-chloro groups have shown remarkable inhibition as showed by the standard drug ciprofloxacin against Escherichia coli and Staphylococcus aureus, respectively. Another compound 4k containing 3,4,5-trimethoxy group also showed similar activity against both these strains. Beside these three potential compounds 4b, 4c, 4k, one more compound 4g containing 4-methyl group showed equivalent inhibition as that of standard drug against E. coli. These categories of compounds are therefore good candidates for developing new effective antibacterial in future.     

β‐Hairpins Generated from Hybrid Peptide Sequences Containing both α‐ and β‐Amino Acids

The incorporation of the β‐amino acid residues into specific positions in the strands and β‐turn segments of peptide hairpins is being systematically explored. The presence of an additional torsion variable about the C(α) C(β) bond (θ) enhances the conformational repertoire in β‐residues. The conformational analysis of three designed peptide hairpins composed of α/β‐hybrid segments is described: Boc‐Leu‐Val‐Val‐^DPro‐β Phe ‐Leu‐Val‐Val‐OMe ( 1 ), Boc‐Leu‐Val‐β Val ‐^DPro‐Gly‐β Leu ‐Val‐Val‐OMe ( 2 ), and Boc‐Leu‐Val‐β Phe ‐Val‐^DPro‐Gly‐Leu‐β Phe ‐Val‐Val‐OMe ( 3 ). 500‐MHz ¹H‐NMR Analysis supports a preponderance of β‐hairpin conformation in solution for all three peptides, with critical cross‐strand NOEs providing evidence for the proposed structures. The crystal structure of peptide 2 reveals a β‐hairpin conformation with two β‐residues occupying facing, non‐H‐bonded positions in antiparallel β‐strands. Notably, βVal(3) adopts a gauche conformation about the C(α) C(β) bond (θ=+65°) without disturbing cross‐strand H‐bonding. The crystal structure of 2 , together with previously published crystal structures of peptides 3 and Boc‐β Phe ‐β Phe ‐^DPro‐Gly‐β Phe ‐β Phe ‐OMe, provide an opportunity to visualize the packing of peptide sheets with local ‘polar segments' formed as a consequence of reversal peptide‐bond orientation. The available structural evidence for hairpins suggests that β‐residues can be accommodated into nucleating turn segments and into both the H‐bonding and non‐H‐bonding positions on the strands.