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Sharma P.,National Institute of Immunology NII | Chitnis C.E.,International Center for Genetic Engineering and Biotechnology
Current Opinion in Microbiology | Year: 2013

The ability of Apicomplexan parasites to invade host cells is key to their survival and pathogenesis. Plasmodium and Toxoplasma parasites share common mechanisms for invasion of host cells. Secretion of microneme and rhoptry proteins, tight junction formation and assembly of an acto-myosin motor are key steps for successful invasion by both parasites. Here, we review our understanding of the molecular basis for these steps. © 2013 Elsevier Ltd.

Majhi M.C.,CSIR - Central Electrochemical Research Institute | Majhi M.C.,Jamia Hamdard University | Behera A.K.,CSIR - Central Electrochemical Research Institute | Kulshreshtha N.M.,CSIR - Central Electrochemical Research Institute | And 4 more authors.
PLoS ONE | Year: 2013

Extremophiles are the microorganisms which can survive under extreme conditions of temperature, pressure, pH, salinity etc. They have gained much attention for their potential role in biotechnological and industrial applications. The large amount of experimental data in the literature is so diverse, that it becomes difficult and time consuming for the researcher to implement it in various areas of research. Therefore, a systematic arrangement of data and redirection in a similar fashion through web interface can assist researchers in analyzing the data as per their requirement. ExtremeDB is a freely available web based relational database which integrates general characteristics, genome-proteome information, industrial applications and recent scientific investigations of the seven major groups of 865 extremophillic microorganisms. The search options are user friendly and analyses tools such as Compare and Extreme BLAST have been incorporated for comparative analysis of two or more extremophiles and determining the sequence similarity of a given protein/nucleotide in relation to other extremophiles respectively. The effort put forth herein in the form of database, would open up new avenues on the potential utility of extremophiles in applied research. ExtremeDB is freely accessible via http://extrem.igib.res.in. © 2013 Majhi et al.

PubMed | National Institute of Immunology NII, Institute of Nuclear Medicine and Allied Sciences and Jamia Hamdard University
Type: | Journal: BioMed research international | Year: 2014

Aim of present study was to develop a solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate, 4:1w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15 hydroxystearate, 1:1w/w], and cosurfactant [diethylene glycol monoethyl ether/polyethylene glycol 300, 1:1w/w] to form stable nanocarrier. The prepared formulation was characterized for droplet size, polydispersity index, and zeta potential. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation and its integrity. Cumulative drug release of prepared formulation through dialysis bag and permeability coefficient through everted gut sac were found to be remarkably higher than the pure drug suspension and commercial intravenous product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay. In vivo systemic exposure of prepared formulation through oral administration was comparable to that of Intaxel in scintigraphy imaging. Our findings suggest that the prepared solid nanoemulsion preconcentrate can be used as an effective oral solid dosage form to improve dissolution and bioavailability of PAC.

PubMed | National Institute of Immunology NII, Indian Institute of Toxicology Research and University of Delhi
Type: | Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | Year: 2016

Rapidly increasing malignant neoplastic disease demands immediate attention. Several dietary compounds have recently emerged as strong anti-cancerous agents. Among, Bromelain (BL), a protease from pineapple plant, was used to enhance its anti-cancerous efficacy using nanotechnology. In lieu of this, hyaluronic acid (HA) grafted PLGA copolymer, having tumor targeting ability, was developed. BL was encapsulated in copolymer to obtain BL-copolymer nanoparticles (NPs) that ranged between 140 to 281nm in size. NPs exhibited higher cellular uptake and cytotoxicity in cells with high CD44 expression as compared with non-targeted NPs. In vivo results on tumor bearing mice showed that NPs were efficient in suppressing the tumor growth. Hence, the formulation could be used as a self-targeting drug delivery cargo for the remission of cancer.

PubMed | National Institute of Immunology NII and University of Delhi
Type: | Journal: The protein journal | Year: 2017

Gamma glutamyl transpeptidase, (GGT) is a ubiquitous protein which plays a central role in glutathione metabolism and has myriad clinical implications. It has been shown to be a virulence factor for pathogenic bacteria, inhibition of which results in reduced colonization potential. However, existing inhibitors are effective but toxic and therefore search is on for novel inhibitors, which makes it imperative to understand the interactions of various inhibitors with the protein in substantial detail. High resolution structures of protein bound to different inhibitors can serve this purpose. Gamma glutamyl transpeptidase from Bacillus licheniformis is one of the model systems that have been used to understand the structure-function correlation of the protein. The structures of the native protein (PDB code 4OTT), of its complex with glutamate (PDB code 4OTU) and that of its precursor mimic (PDB code 4Y23) are available, although at moderate/low resolution. In the present study, we are reporting the preliminary analysis of, high resolution X-ray diffraction data collected for the co-crystals of B. licheniformis, Gamma glutamyl transpeptidase, with its inhibitor, Acivicin. Crystals belong to the orthorhombic space group P2

Bhardwaj I.,Indian Institute of Technology Delhi | Jha D.,National Institute of Immunology NII | Admane P.,National Institute of Immunology NII | Panda A.K.,National Institute of Immunology NII | Haridas V.,Indian Institute of Technology Delhi
Bioorganic and Medicinal Chemistry Letters | Year: 2016

A series of tryptophan-based peptides W1a, b-W4a, b, with diverse architectures were designed and synthesized. These tryptophan containing peptides can self-assemble to spherical particle. This self-assembled system was demonstrated to encapsulate rhodamine B and penetrate the cell membrane. © 2015 Elsevier Ltd. All rights reserved.

PubMed | National Institute of Immunology NII and Indian Institute of Technology Delhi
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2016

A series of tryptophan-based peptides W1a, b-W4a, b, with diverse architectures were designed and synthesized. These tryptophan containing peptides can self-assemble to spherical particle. This self-assembled system was demonstrated to encapsulate rhodamine B and penetrate the cell membrane.

Kapoor R.,National Institute of Immunology NII | Arora S.,National Institute of Immunology NII | Ponia S.S.,National Institute of Immunology NII | Kumar B.,National Institute of Immunology NII | And 2 more authors.
Biochemical Journal | Year: 2015

HIV-1 relies heavily on the host cellular machinery for its replication. During infection, HIV-1 is known to modulate the host-cell miRNA profile. One of the miRNAs, miR-34a, is up-regulated by HIV-1 in T-cells as suggested by miRNA microarray studies. However, the functional consequences and the mechanism behind this phenomenon were not explored. The present study shows that HIV-1 enhances miR-34a in a time-dependent manner in T-cells. Our overexpression and knockdown-based experimental results suggest that miR-34a promotes HIV-1 replication in T-cells. Hence, there is a positive feedback loop between miR-34a and HIV-1 replication. We show that the mechanism of action of miR-34a in HIV-1 replication involves a cellular protein, the phosphatase 1 nuclear-targeting subunit (PNUTS). PNUTS expression levels decrease with the progression of HIV-1 infection in T-cells. Also, the overexpression of PNUTS potently inhibits HIV-1 replication in a dose-dependent manner. We report for the first time that PNUTS negatively regulates HIV-1 transcription by inhibiting the assembly of core components of the transcription elongation factor P-TEFb, i.e. cyclin T1 and CDK9. Thus, HIV-1 increases miR-34a expression in cells to overcome the inhibitory effect of PNUTS on HIV-1 transcription. So, the present study provides new mechanistic details with regard to our understanding of a complex interplay between miR-34a and the HIV-1 transcription machinery involving PNUTS. © 2015 Authors.

Prakash S.,Indian Institute of Science | Prakash S.,Chandigarh Institute of Microbial Technology | Sundd M.,National Institute of Immunology NII | Guptasarma P.,Indian Institute of Science | Guptasarma P.,Chandigarh Institute of Microbial Technology
PLoS ONE | Year: 2014

Pyrococcus furiosus rubredoxin (PfRd), a small, monomeric, 53 residues-long, iron-containing, electron-transfer protein of known structure is sometimes referred to as being the most structurally-stable protein known to man. Here, using a combination of mutational and spectroscopic (CD, fluorescence, and NMR) studies of differently made holo- and apo-forms of PfRd, we demonstrate that it is not the presence of iron, or even the folding of the PfRd chain into a compact well-folded structure that causes holo-PfRd to display its extraordinary thermal stability, but rather the correct iron binding-guided packing of certain residues (specifically, Trp3, Phe29, Trp36, and also Tyr10) within a tight aromatic cluster of six residues in PfRd's hydrophobic core. Binding of the iron atom appears to play a remarkable role in determining subtle details of residue packing, forcing the chain to form a hyper-thermally stable native structure which is kinetically stable enough to survive (subsequent) removal of iron. On the other hand, failure to bind iron causes the same chain to adopt an equally well-folded native-like structure which, however, has a differently-packed aromatic cluster in its core, causing it to be only as stable as any other ordinary mesophile-derived rubredoxin. Our studies demonstrate, perhaps for the very first time ever that hyperthermal stability in proteins can owe to subtle differences in residue packing vis a vis mesostable proteins, without there being any underlying differences in either amino acid sequence, or bound ligand status. © 2014 Prakash et al.

Agarwal K.,National Institute of Immunology NII | Kaul R.,National Institute of Immunology NII | Garg M.,National Institute of Immunology NII | Shajahan A.,National Institute of Immunology NII | And 2 more authors.
Journal of the American Chemical Society | Year: 2013

Mucin-type O-glycans form one of the most abundant and complex post-translational modifications (PTM) on cell surface proteins that govern adhesion, migration, and trafficking of hematopoietic cells. Development of targeted approaches to probe functions of O-glycans is at an early stage. Among several approaches, small molecules with unique chemical functional groups that could modulate glycan biosynthesis form a critical tool. Herein, we show that metabolism of peracetyl N-acyl-d-galactosamine derivatives carrying an N-thioglycolyl (Ac5GalNTGc, 1) moiety - but not N-glycolyl (Ac 5GalNGc, 2) and N-acetyl (Ac4GalNAc, 3) - through the N-acetyl-d-galactosamine (GalNAc) salvage pathway induced abrogation of MAL-II and PNA epitopes in Jurkat cells. Mass spectrometry of permethylated O-glycans from Jurkat cells confirmed the presence of significant amounts of elaborated O-glycans (sialyl-T and disialyl-T) which were inhibited upon treatment with 1. O-Glycosylation of CD43, a cell surface antigen rich in O-glycans, was drastically reduced by 1 in a thiol-dependent manner. By contrast, only mild effects were observed for CD45 glycoforms. Direct metabolic incorporation of 1 was confirmed by thiol-selective Michael addition reaction of immunoprecipitated CD43-myc/FLAG. Mechanistically, CD43 glycoforms were unperturbed by peracetylated N-(3-acetylthiopropanoyl) (4), N-(4-acetylthiobutanoyl) (5), and N-methylthioacetyl (6) galactosamine derivatives, N-thioglycolyl-d-glucosamine (7, C-4 epimer of 1), and α-O-benzyl 2-acetamido-2-deoxy-d- galactopyranoside (8), confirming the critical requirement of both free sulfhydryl and galactosamine moieties for inhibition of mucin-type O-glycans. Similar, yet differential, effects of 1 were observed for CD43 glycoforms in multiple hematopoietic cells. Development of small molecules that could alter glycan patterns in an antigen-selective and cell-type selective manner might provide avenues for understanding biological functions of glycans. © 2013 American Chemical Society.

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