Tuniki Balaraju

A series of C-7 substituted-2-morpholino-N-(pyridin-2-ylmethyl)quinazolin-4-amine have been synthesized and biochemical assay was examined against α-glucosidase function inhibition activity. A structure activity and structure property relationship study was experimented to surface the new hit compound. This study led to the identification of C-7substituted quinazolines with minimum inhibitory concentrations (MICs) in the preffered micromolar range in addition with interesting physicochemical properties. Biological evaluation yielded eight analogs which rose with significant α-glucosidase inhibition potency (IC50 values < 2 μM, where reference compound (Acarbose) potency value is IC50 = 0.586 uM) and could be promising candidates for further lead optimization.

The present studies report the synthesis of a novel graft copolymer “polymethyl methacrylate-grafted oatmeal” (OAT-g-PMMA) using “conventional” technique. Grafting of PMMA chains on the backbone of parent biopolymer (oatmeal) was confirmed through various physicochemical techniques like intrinsic viscosity, FTIR, elemental analysis (C, H, N, S and O), scanning electron microscopy, thermal gravimetric analysis, number-average molecular weight, solubility, ¹³C-CP/MAS solid-state NMR spectroscopy and P-XRD. The intrinsic viscosity of oatmeal substantially improved after grafting of PMMA chains. The grafted biopolymers were assessed for its implication as a potential flocculant by standard “jar test” and “settling test” protocol. Flocculation characteristics of the synthesized OAT-g-PMMA were compared with parent biopolymer (oatmeal) and alum in 0.25 wt.% kaolin suspension and then in municipal wastewater through standard “jar test” protocol which showed encouraging results.

We report soft-oxometalate catalytic systems based on various metal oxide catalysts to oxidize H ₂ O and utilize the generated H ⁺ s and e ⁻ s for reduction of CO ₂ with a TON of 1366 (effectively 1.4 x 10 ⁶ ).

Calsequestrin (CASQ) exists as two distinct isoforms CASQ1 and CASQ2 in all vertebrates. Although the isoforms exhibit unique functional characteristic, the structural basis for the same is yet to be fully defined. Interestingly, the C‐terminal region of the two isoforms exhibit significant differences both in length and amino acid composition; forming Dn‐motif and DEXn‐motif in CASQ1 and CASQ2, respectively. Here, we investigated if the unique C‐terminal motifs possess Ca²⁺‐sensitivity and affect protein function. Sequence analysis shows that both the Dn‐ and DEXn‐motifs are intrinsically disordered regions (IDRs) of the protein, a feature that is conserved from fish to man. Using purified synthetic peptides, we show that these motifs undergo distinctive Ca²⁺‐mediated folding suggesting that these disordered motifs are Ca²⁺‐sensitivity. We generated chimeric proteins by swapping the C‐terminal portions between CASQ1 and CASQ2. Our studies show that the C‐terminal portions do not play significant role in protein folding. An interesting finding of the current study is that the switching of the C‐terminal portion completely reverses the polymerization kinetics. Collectively, these data suggest that these Ca²⁺‐sensitivity IDRs located at the back‐to‐back dimer interface influence isoform‐specific Ca²⁺‐dependent polymerization properties of CASQ. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 15–22, 2015.

Computer‐aided approaches coupled with medicinal chemistry were used to explore novel carbocyclic nucleosides as potential anti‐hepatitis C virus (HCV) agents. Conformational analyses were carried out on 6‐amino‐1H‐pyrazolo[3,4‐d]pyrimidine (6‐APP)‐based carbocyclic nucleoside analogues, which were considered as nucleoside mimetics to act as HCV RNA‐dependent RNA polymerase (RdRp) inhibitors. Structural insight gained from the modeling studies revealed the molecular basis behind these nucleoside mimetics. The rationally chosen 6‐APP analogues were prepared and evaluated for anti‐HCV activity. RdRp SiteMap analysis revealed the presence of a hydrophobic cavity near C7 of the nucleosides; introduction of bulkier substituents at this position enhanced their activity. Herein we report the identification of an iodinated compound with an EC₅₀ value of 6.6 μM as a preliminary anti‐HCV lead.

Biophysical studies have shown that each molecule of calsequestrin 1 (CASQ1) can bind about 70–80 Ca²⁺ ions. However, the nature of Ca²⁺-binding sites has not yet been fully characterized. In this study, we employed in silico approaches to identify the Ca²⁺ binding sites and to understand the molecular basis of CASQ1–Ca²⁺ recognition. We built the protein model by extracting the atomic coordinates for the back-to-back dimeric unit from the recently solved hexameric CASQ1 structure (PDB id: 3UOM) and adding the missing C-terminal residues (aa350–364). Using this model we performed extensive 30 ns molecular dynamics simulations over a wide range of Ca²⁺ concentrations ([Ca²⁺]). Our results show that the Ca²⁺-binding sites on CASQ1 differ both in affinity and geometry. The high affinity Ca²⁺-binding sites share a similar geometry and interestingly, the majority of them were found to be induced by increased [Ca²⁺]. We also found that the system shows maximal Ca²⁺-binding to the CAS (consecutive aspartate stretch at the C-terminus) before the rest of the CASQ1 surface becomes saturated. Simulated data show that the CASQ1 back-to-back stacking is progressively stabilized by the emergence of an increasing number of hydrophobic interactions with increasing [Ca²⁺]. Further, this study shows that the CAS domain assumes a compact structure with an increase in Ca²⁺ binding, which suggests that the CAS domain might function as a Ca²⁺-sensor that may be a novel structural motif to sense metal. We propose the term “D_n-motif” for the CAS domain.