Solution studies on trace metal ion interactions with adenine as primary ligand and 5-halouracils as secondary ligands

The interaction of trace metal ions, viz. Mn^II, Co^II, Ni^II, Cu^II, Zn^II and Cd^II with adenine (A) as primary ligand and 5-halouracils, viz. 5-bromouracil (5BrU) and 5-iodouracil (5IU) as secondary ligands (L) has been studied at 25±0.1°C and at constant ionic strength (=0.1M NaNO₃), in an aqueous medium using Bjerrum–Calvin's pH-titration technique as adopted by Irving and Rossotti for binary (ML), and by Chidambaram and Bhattacharya for ternary (MAL) systems respectively. The experimental pH-titration data were analyzed with the aid of the BEST computer program in order to evaluate formation constants of various intermediate complex species formed in binary and ternary systems involving nucleobases (viz. A, 5BrU and 5IU). The relative stability of each ternary complex was compared with that of the corresponding binary complexes in terms of logK values.     

A Cell-Culture Technique to Encode Glyco-Nanoparticles Selectivity

Nanoparticles (NPs) embedded with bioactive ligands such as carbohydrates, peptides, and nucleic acid have emerged as a potential tool to target biological processes. Traditional in vitro assays performed under statistic conditions may result in non-specific outcome sometimes, mainly because of the sedimentation and self-assembly nature of NPs. Inverted cell-culture assay allows for flexible and accurate detection of the receptor-mediated uptake and cytotoxicity of NPs. By combining this technique with glyco-gold nanoparticles, cellular internalization and cytotoxicity were investigated. Regioselective glycosylation patterns and shapes of the NPs could tune the receptors′ binding affinity, resulting in precise cellular uptake of gold nanoparticles (AuNPs). Two cell lines HepG2 and HeLa were probed with galactosamine-embedded fluorescent AuNPs, revealing significant differences in cytotoxicity and uptake mechanism in upright and invert in vitro cell-culture assay, high-specificity toward uptake, and allowing for a rapid screening and optimization technique.     

One‐pot oxidation of aromatic and cyclic hydrocarbons using the Au (III) and Pd (II) catalyst under microwave irradiation

We report here in highly efficient one‐pot catalytic system which utilizes in situ generated sodium ferrate for the oxidation of aromatic and cyclic hydrocarbons in the presence of Au (III) and Pd (II) metal ions catalyst under ecofriendly green synthetic method. Results of these studies revealed that Au (III) catalytic system gave higher yield as compared with Pd (II) catalytic system because of the higher electrode potential of Au(III) than Pd(II). All compounds were characterized by infrared and NMR spectral analysis. Copyright © 2016 John Wiley & Sons, Ltd.     

Photo-Controlled Gating of Selective Bacterial Membrane Interaction and Enhanced Antibacterial Activity for Wound Healing

Reversible biointerfaces are essential for on-demand molecular recognition to regulate stimuli-responsive bioactivity such as specific interactions with cell membranes. The reversibility on a single platform allows the smart material to kill pathogens or attach/detach cells. Herein, we introduce a 2D-MoS₂ functionalized with cationic azobenzene that interacts selectively with either Gram-positive or Gram-negative bacteria in a light-gated fashion. The trans conformation ( trans -Azo-MoS₂ ) selectively kills Gram-negative bacteria, whereas the cis form ( cis -Azo-MoS₂ ), under UV light, exhibits antibacterial activity against Gram-positive strains. The mechanistic investigation indicates that the cis -Azo-MoS₂ exhibits higher affinity towards the membrane of Gram-positive bacteria compared to trans -Azo-MoS₂ . In case of Gram-negative bacteria, trans -Azo-MoS₂ internalizes more efficiently than cis -Azo-MoS₂ and generates intracellular ROS to kill the bacteria. While the trans -Azo-MoS₂ exhibits strong electrostatic interactions and internalizes faster into Gram-negative bacterial cells, cis -Azo-MoS₂ primarily interacts with Gram-positive bacteria through hydrophobic and H-bonding interactions. The difference in molecular mechanism leads to photo-controlled Gram-selectivity and enhanced antibacterial activity. We found strain-specific and high bactericidal activity (minimal bactericidal concentration, 0.65 μg/ml) with low cytotoxicity, which we extended to wound healing applications. This methodology provides a single platform for efficiently switching between conformers to reversibly control the strain-selective bactericidal activity regulated by light.     

Multivalent Sialosides: A Tool to Explore the Role of Sialic Acids in Biological Processes

Sialic acids (Sias) are fascinating nine‐carbon monosaccharides that are primarily found on the terminus of the oligosaccharide chains of glycoproteins and glycolipids on cell surfaces. These Sias undergo a variety of structural modifications at their hydroxy and amine positions, thereby resulting in structural diversity and, hence, coordinating a variety of biological processes. However, deciphering the structural functions of such interactions is highly challenging, because the monovalent binding of Sias is extremely weak. Over the last decade, several multivalent Sia ligands have been synthesized to modulate their binding affinity with proteins/lectins. In this Minireview, we highlight recent developments in the synthesis of multivalent Sia probes and their potential applications. We will discuss four key multivalent families, that is, polymers, dendrimers, liposomes, and nanoparticles, and will emphasize the major parameters that are essential for the specific interactions of these molecules with proteins in biological systems.     

Carbonyl Sulfide (COS) Donor Induced Protein Persulfidation Protects against Oxidative Stress

The emergence of hydrogen sulfide (H₂S) as an important signalling molecule in redox biology with therapeutic potential has triggered interest in generating this molecule within cells. One strategy that has been proposed is to use carbonyl sulfide (COS) as a surrogate for hydrogen sulfide. Small molecules that generate COS have been shown to produce hydrogen sulfide in the presence of carbonic anhydrase, a widely prevalent enzyme. However, other studies have indicated that COS may have biological effects which are distinct from H₂S. Thus, it would be useful to develop tools to compare (and contrast) effects of COS and H₂S. Here we report enzyme‐activated COS donors that are capable of inducing protein persulfidation, which is symptomatic of generation of hydrogen sulfide. The COS donors are also capable of mitigating stress induced by elevated reactive oxygen species. Together, our data suggests that the effects of COS parallel that of hydrogen sulfide, laying the foundation for further development of these donors as possible therapeutic agents.     

Biochemical and Biophysical Characterisation of the Hepatitis E Virus Guanine-7-Methyltransferase

Hepatitis E virus (HEV) is an understudied pathogen that causes infection through fecal contaminated drinking water and is prominently found in South Asian countries. The virus affects ~20 million people annually, leading to ~60,000 infections per year. The positive-stranded RNA genome of the HEV genotype 1 has four conserved open reading frames (ORFs), of which ORF1 encodes a polyprotein of 180 kDa in size, which is processed into four non-structural enzymes: methyltransferase (MTase), papain-like cysteine protease, RNA-dependent RNA polymerase, and RNA helicase. MTase is known to methylate guanosine triphosphate at the 5′-end of viral RNA, thereby preventing its degradation by host nucleases. In the present study, we cloned, expressed, and purified MTase spanning 33–353 amino acids of HEV genotype 1. The activity of the purified enzyme and the conformational changes were established through biochemical and biophysical studies. The binding affinity of MTase with magnesium ions (Mg²⁺) was studied by isothermal calorimetry (ITC), microscale thermophoresis (MST), far-UV CD analysis and, fluorescence quenching. In summary, a short stretch of nucleotides has been cloned, coding for the HEV MTase of 37 kDa, which binds Mg²⁺ and modulate its activity. The chelation of magnesium reversed the changes, confirming its role in enzyme activity.     

Small x phenomenology on gluon evolution through the BFKL equation in light of a constraint in multi-Regge kinematics

We investigate the impact of so-called kinematic constraint on gluon evolution at small x.Implanting the constraint on the real emission term of the gluon ladder diagram, we obtain an integro-differential form of the Balitsky-Fadin-Kuraev-Lipatov(BFKL) equation. Later we solve the equation analytically using the method of characteristics. We sketch the Bjorken x and transverse momentum k_t~2 dependence of our solution of unintegrated gluon distributions f (x,k_t~2) in the kinematic constraint supplemented BFKL equation and contrasted the same with the original BFKL equation. Then we extract the integrated gluon density xg(x, Q~2) from unintegrated gluon distributions f (x,k_t~2) and compared our theoretical prediction with that of global data fits, namely NNPDF3.1 sx and CT14. Finally we illustrate the phenomenological implication of our solution for unintegrated gluon distribution f (x,k_T~2) towards exploring high precision HERA DIS data by the theoretical prediction of proton structure functions(F_2 and F_L).