Base-Pairing Properties of Double-Headed Nucleotides

Nucleotides that contain two nucleobases (double-headed nucleotides) have the potential to condense the information of two separate nucleotides into one. This presupposes that both bases must successfully pair with a cognate strand. Here, double-headed nucleotides that feature cytosine, guanine, thymine, adenine, hypoxanthine, and diaminopurine linked to the C2′-position of an arabinose scaffold were developed and examined in full detail. These monomeric units were efficiently prepared by convergent synthesis and incorporated into DNA oligonucleotides by means of the automated phosphoramidite method. Their pairing efficiency was assessed by UV-based melting-temperature analysis in several contexts and extensive molecular dynamics studies. Altogether, the results show that these double-headed nucleotides have a well-defined structure and invariably behave as functional dinucleotide mimics in DNA duplexes.     

Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP

The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated.     

Rheological characteristics of CeO2, Al2O3 and their hybrid mixture in ethylene glycol base fluid in the wide range of temperature and concentration

Journal of Thermal Analysis and Calorimetry - In the present work, the rheological behaviour of three different categories of nanofluid samples, 25 nm CeO2/EG, 13 nm Al2O3/EG and...     

Flow-driven Surface Instabilities of Tubular Chitosan Hydrogel

Spatial structures break their symmetry under the influence of shear stress arising from fluid flow. Here, we present surface instabilities appearing on chitosan tubes when an acidic solution of chitosan with various molecular weight is injected into a pool of sodium hydroxide solution. At slow flow rates wrinkle-to-fold transition takes place along the direction of the flow yielding a banded structure. For greater injection rates we observe coexisting modes of wrinkles and folds which are stabilized to periodic wrinkles when the alkaline concentration is increased. The instabilities are characterized by the scaling laws of the pattern wavelength and amplitude with the tube characteristics. Our experimental adaptation of mechanical instabilities provides a new in situ method to create soft biomaterials with the desired surface morphology without the use of any prefabricated templates.     

Electrochemical studies of novel olivine-layered (LiFePO4-Li2MnO3) dual composite as an alternative cathode material for lithium-ion batteries

Journal of Solid State Electrochemistry - In the present work, olivine-layered composites, i.e., LiFePO4-Li2MnO3, are successfully synthesized in the form of a single monolithic electrode and layer...     

Out-of-plane low field anisotropic magnetoresistance in Nd0.51Sr0.49MnO3 thin films

A comparative study of the out-of-plane anisotropic magnetoresistance (AMR) in single crystalline and polycrystalline thin films of phase separated manganite Nd_0.51Sr_0.49MnO₃ has been carried out. On-axis DC magnetron sputtering was used to deposit the single crystalline films (30 and 100 nm in thickness) on single crystal (0 0 1) LaAlO₃ (LAO) and polycrystalline films (100 nm) on (1 0 0) Yttrium-stabilized ZrO₂ (YSZ) substrates. The in-plane and out-of-plane magnetotransport properties of these films differ significantly. A large low field AMR is observed in all the films. AMR shows a peak below the insulator-metal transition temperature in the single crystalline films, while the same increases monotonically in the polycrystalline film. Relatively larger low field AMR (∼20% at T=78 K and H=1.7 kOe) in the polycrystalline films suggests the dominance of the shape anisotropy.     

Optimized synthesis of [3-N]-labeled uridine phosphoramidites

A short and high-yielding synthetic route to [3-¹⁵N]-labeled uridine phosphoramidite 1 (26% overall yield from uridine) has been developed. This will enable automated synthesis of isotopically labeled RNA strands and facilitate their use in structural studies.