Biology subjects

Neha,

Publications and source records attributed to Neha,.

4 recordsLinked to original sources

bioRxiv2023

Discovery & Evaluation of novel fluorescence molecules for selective recognition of G-quadruplexes structure

Currently, G-quadruplex structure targeting strategies are considered as a promising anticancer approach. In the search of selective and potent G-quadruplex binders, Here we discuss an analysis of a few chroman derivatives ligands: (A) chroman 7-[2-pyrrolo]-pyrrole-[1,2-a]12H pyrrolino[2,3-b]chroman-4-one, and (C) 4-methyl-7-[2-pyrrolo]-pyrrole[1,2-a]12H pyrrolino[2,3-b]chroman-4-one and their respective borondifluoride complexes B and D as a quadruplex targeting compounds which found to stabilize G-quadruplex structure. To investigate the binding characteristics of these molecules with G-quadruplex vs. duplex selectivity, In vitro biophysical studies were performed by steady-state fluorescence, UV-visible titration, fluorescent TO displacement assay, CD thermal melting, circular dichroism spectroscopy, and cellular imaging by employing both telomeric and PRCC G-quadruplex forming sequences. Our investigation shows that these chromam ligands and their complexes are able to selectively bind and stabilize parallel and mixed hybrid topology of G-quadruplex both In vitro and in cellular conditions. A molecular docking study also suggests the binding of these compounds with G-quadruplex conformation. Collectively our study suggests these chroman complexes as a potentially useful fluorescent chemical product for G-quadruplex specific ligands and expands an option for G-quadruplex targeting ligands.

biochemistry↗

bioRxiv2023

Discovery of novel G-quadruplex stabilizing compounds from medicinal plant & Evaluates their cellular toxicity

G-Quadruplexes (G4Q) are higher-order, four-stranded structures that can be formed by repeated guanine tracts in human genomes. In this study, we used a structure-based virtual screening of phytomolecules derived from medicinal plants in order to discover new natural DNA G4Q binders. The top 40 ligands were sorted out based on binding affinity values after completing a docking study on 314 phytomolecule samples with parallel and mixed hybrid structure. Further Thermal melting, circular dichroism, and fluorescence displacement experiment was used as a preliminary screening tool to determine the potential stabilizing properties of {beta}-sitosterol-{beta}-D-glucoside, and Glabrolide. The cytotoxicity experiments were conducted on HEK293T cells and found that both of the tested phyto molecules are non-toxic for up to 150 M concentration. Based on their cytotoxic experiments at the suggested high concentration, these phyto molecules may potentially be employed as G-Quadruplex targets in future research or applications. These results suggest that the plant may be a "lead" in the future for the development of novel therapies for diseases.

biochemistry↗

bioRxiv2023

Exploring G-quadruplex structure in PRCC-TFE3 fusion Oncogene: Plausible use as anti cancer therapy for translocation Renal cell carcinoma (tRCC)

The TFE3 fusion gene, byproduct of Xp11.2 translocation, is the diagnostic marker for translocation renal cell carcinoma (tRCC). Absence of any clinically recognized therapy for tRCC, pressing a need to create novel and efficient therapeutic approaches. Previous studies shown that stabilization of the G-quadruplex structure in oncogenes suppresses their expression machinery. To combat the oncogenesis caused by fusion genes, our objective is to locate and stabilize the G-quadruplex structure within the PRCC-TFE3 fusion gene. Using the Quadruplex- forming G Rich Sequences (QGRS) mapper and the Non-B DNA motif search tool (nBMST) online server, we found putative G-quadruplex forming sequences (PQS) in the PRCC-TFE3 fusion gene. Circular dichroism demonstrating a parallel G-quadruplex in the targeted sequence. Fluorescence and UV-vis spectroscopy results suggest that pyridostatin binds to this newly discovered G-quadruplex. The PCR stop assay, as well as transcriptional or translational inhibition by PQS, revealed that stable G-quadruplex formation affects biological processes. Confocal microscopy of HEK293T cells transfected with the fusion transcript confirmed G- quadruplexes formation in cell. This investigation may shed light on G-quadruplexs functions in fusion genes and may help in the development of therapies specifically targeted against fusion oncogenes, which would enhance the capability of current tRCC therapy approach.

molecular biology↗

bioRxiv2021

The influence of new SARS-CoV-2 variant Omicron (B.1.1.529) on vaccine efficacy, its correlation to Delta Variants: a computational approach

The newly discovered COVID variant B.1.1.529 in Botswana has more than 30 mutations in spike and many other in non-spike proteins, far more than any other SARS-CoV-2 variant accepted as a variant of concern by the WHO and officially named Omicron, and has sparked concern among scientists and the general public. Our findings provide insights into structural modification caused by the mutations in the Omicrons receptor-binding domain and look into the effects on interaction with the hosts neutralising antibodies CR3022, B38, CB6, P2B-2F6, and REGN, as well as ACE2R using an in silico approach. We have employed secondary structure prediction, structural superimposition, protein disorderness, molecular docking, and MD simulation to investigate host-pathogen interactions, immune evasion, and transmissibility caused by mutations in the RBD region of the spike protein of the Omicron variant and compared it to the Delta variants (AY.1, AY.2, & AY.3) and wild type. Computational analysis revealed that the Omicron variant has a higher binding affinity for the human ACE2 receptor than the wild and Delta (AY.1 and AY.2 strains), but lower than the Delta AY.3 strain. MD simulation and docking analysis suggest that the omicron and Delta AY.3 were found to have relatively unstable and compact RBD structures and hampered interactions with antibodies more than wild and Delta (AY.1 and AY.2), which may lead to relatively more pathogenicity and antibody escape. In addition, we observed lower binding affinity of Omicron for human monoclonal antibodies (CR3022, B38, CB6, and P2B2F6) when compared to wild and Delta (AY.1 & AY.2). However, the binding affinity of Omicron RBD variants for CR3022, B38, and P2B2F6 antibodies is lower as compared to Delta AY.3, which might promote immune evasion and reinfection and needs further experimental investigation.

bioinformatics↗