School Of Basic And Applied Sciences

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    Macromolecular crowding-induced molten globule states of the alkali pH-denatured proteins
    (Elsevier B.V., 2018) Kumar, Rajesh; Kumar, Rajesh; Sharma, Deepak; Garg, Mansi; Kumar, Vinay; Agarwal, Mukesh Chand
    Structural and molecular properties extracted from circular dichroism (CD), tryptophan fluorescence and 1-anilino-8-napthalene sulfonate (ANS) binding experiments suggest that the high concentration of synthetic crowding agents (dextran 40, dextran 70 and ficoll 70) stabilizes and refolds the base-denatured ferricytochrome c (Ferricyt c) and lysozyme (Lyz) at pH 12.9 (±0.1) to molten globule (MG) states (C B -states). These results further revealed that the C B -states resemble the generic properties of MG-states. Thermodynamic analysis of thermal denaturation curves of base-denatured Ferricyt c and Lyz at pH 12.9 (±0.1) under variable concentrations of crowding agents (dextran 40, dextran 70 and ficoll 70) revealed that the crowder presence increases the thermal stability of base-denatured proteins and also prevents the cold denaturation of Ferricyt c. The results further showed that the nature, size and shape of crowder influence the crowding-mediated increase in secondary structure stabilization and thermal stability of base-denatured Ferricyt c and Lyz. Analysis of kinetic and thermodynamic parameters measured for CO association reaction of alkaline ferrocytochrome c (Ferrocyt c) at pH 12.9 (±0.1) under variable concentrations of crowding agents (dextran 40, dextran 70 and ficoll 70) revealed that the crowder presence reduces the level of structural fluctuation of M80-containing ?-loop that control CO association to alkaline Ferrocyt c. - 2018 Elsevier B.V.
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    Pyrazoloquinazolines: Synthetic strategies and bioactivities
    (2015) Garg, Mansi; Chauhan, Monika; Singh, Pankaj Kumar; Singh, Pankaj Kumar; Alex, Jimi Marin; Kumar, Raj
    Numerous N-heterocycles are indisputably evidenced to exhibit myriad biological activities. In the recent past, attempts made to condense the various heterocycles have resulted in derivatives possessing better bioactivities. Among many such condensed heterocycles, pyrazoloquinazolines have managed to hold the attention of many researchers, owing to the broad spectrum of activities they portray. This review is the first of its kind to congregate the various pyrazoloquinazolines reported until now and categorizes these structurally isomeric classes into eleven different groups based on the fusion pattern of the ring such as [1,5-c], [5,1-b], [4,3-h], etc. Furthermore, this review is a concerted effort to highlight design, synthetic strategies as well as biological activities of each class of this condensed heterocycle. Structure-activity relationship studies and in silico approaches wherever reported have also been discussed. In addition, manuscript also offers scope for design, synthesis and generation of libraries of unreported classes of pyrazoloquinazolines for the biological evaluation. Copyright ? 2014 Elsevier Masson SAS. All rights reserved.
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    Identification of new insulin growth factor receptor-1 (IGF-1R) inhibitors via exploring ATPas kinase domain of IGF-1R through virtual screening
    (Birkhauser Boston, 2017) Garg, Mansi; Chauhan, Monika; Kumar, Raj
    Insulin growth factor receptor-1 is a trans-membrane tyrosine kinase receptor that mediates the polypeptide protein hormone insulin growth factor-1, responsible for normal function and growth of human cells. The overexpression of insulin growth factor receptor-1 has been associated with a variety of cancers. A number of small molecule inhibitors of insulin growth factor receptor-1 are discovered by various researchers but all of them get failed in preclinical trials due to less potency and resistance. In the present paper, we have identified new insulin growth factor receptor-1 inhibitors through virtual screening based on ATPase kinase domain having phosphate, sugar and hydrophobic regions lined with amino acid residues such as Asp 1150, Lys 1003, Phe 1124 and Lys 1033. A total of 7659 compounds were selected from PubChem database. Then on applying, the rule of five, 4482 compounds were enlisted and downloaded. Further on performing high throughput virtual screening, standard precision and extra precision three best scoring compounds were identified, which could be taken further for drug development. ? 2016, Springer Science+Business Media New York.