Publications by authors named "Ramendra Pati Pandey"

16 Publications

  • Page 1 of 1

Identification and validation of potent Mycobacterial proteasome inhibitor from Enamine library.

J Biomol Struct Dyn 2021 May 6:1-11. Epub 2021 May 6.

Centre for Drug Design Discovery and Development (C4D), SRM University, Delhi NCR, Sonepat, India.

As a consequence of present status of tuberculosis (TB) it is the obligation to develop novel targets and potential drugs so that rate of drug resistant TB can be declined. Mycobacterium proteasome is considered to be significant target for the purpose of drug designing as it is responsible for resisting the effect of NO (nitric oxide) immune system defence mechanism against the bacterial cells. Small compounds library from Enamine database has already been tested using virtual screening and molecular docking studies. Further a reanalysis with two picked out significant compounds Z1020863610, Z106766984 was carried out using molecular dynamic simulation studies and in vitro validations ( susceptibility assay, enzyme inhibition assay and MTT assay). outcome that two inhibiters were interacting at the active site pocket of receptor with high stability, was found to be very consistent with results. So it was conferred that compounds (Z1020863610, Z106766984) are potential lead for future process of drug development ( testing and clinical trials).Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1914173DOI Listing
May 2021

Gefitinib Results in Robust Host-Directed Immunity Against Infection Through Proteo-Metabolomic Reprogramming.

Front Immunol 2021 31;12:648710. Epub 2021 Mar 31.

Infection and Immunobiology, Translational Health Science and Technology Institute, Faridabad, India.

The global rise of antibiotic-resistant strains of has necessitated the development of alternative therapeutic strategies. Recent studies have shown that targeting host factors may provide an alternative approach for the treatment of intracellular pathogens. Host-directed therapy (HDT) modulates host cellular factors that are essential to support the replication of the intracellular pathogens. In the current study, we identified Gefitinib as a potential host directed therapeutic drug against . Further, using the proteome analysis of -infected macrophages, we identified EGFR, a host factor, promoting intracellular survival of mTOR-HIF-1α axis. Blocking of EGFR, mTOR or HIF-1α inhibits the intracellular survival of within the macrophages and in mice. Global proteo-metabolomics profiling indicated the upregulation of host factors predominantly associated with ATP turn over, glycolysis, urea cycle, which ultimately promote the activation of EGFR-HIF1α signaling upon infection. Importantly, inhibition of EGFR and HIF1α restored both proteomics and metabolomics changes caused by infection. Taken together, this study identifies Gefitinib as a host directed drug that holds potential translational values against infection and might be useful for the treatment of other intracellular infections.
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http://dx.doi.org/10.3389/fimmu.2021.648710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044459PMC
March 2021

Multiple clades of Husavirus in South America revealed by next generation sequencing.

PLoS One 2021 23;16(3):e0248486. Epub 2021 Mar 23.

Departamento de Moléstias Infecciosas e Parasitárias, Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Husavirus (HuV) is an unclassified virus of the order Picornavirales that has already been identified worldwide in various locations. The genetic, epidemiological, and pathogenic characteristics are, however, little understood. In children with acute gastroenteritis, this study used next-generation sequencing to recognize unknown sources of viruses. In particular, 251 fecal samples obtained from individuals were sequenced in southern, northeastern, and northern Brazil. all samples were also analyzed using culture methods and parasitological tests to classify other enteric pathogens such as bacteria, parasites, and viruses. 1.9% of the samples tested positive for HuV, for a total of 5 positive children, with a mean age of 2 year, with three males and two females. Detailed molecular characterization of full genomes showed that Brazilian HuVs' nucleotide divergence is less than 11%. The genetic gap between Brazilian sequences and the closest HuV reported previously, on the other hand, is 18%. The study showed that Brazilian sequences are closely related to the HuV defined in Viet Nam in 2013, further characterization based on phylogenetics. At least two divergent clades of HuV in South America were also seen in the phylogenetic study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248486PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987173PMC
March 2021

Guapiaçu virus, a new insect-specific flavivirus isolated from two species of Aedes mosquitoes from Brazil.

Sci Rep 2021 Feb 25;11(1):4674. Epub 2021 Feb 25.

Institute of Tropical Medicine, University of São Paulo, São Paulo, SP, 05403-000, Brazil.

Classical insect-flaviviruses (cISFVs) and dual host-related insect-specific flavivirus (dISFV) are within the major group of insect-specific flavivirus. Remarkably dISFV are evolutionarily related to some of the pathogenic flavivirus, such as Zika and dengue viruses. The Evolutionary relatedness of dISFV to flavivirus allowed us to investigate the evolutionary principle of host adaptation. Additionally, dISFV can be used for the development of flavivirus vaccines and to explore underlying principles of mammalian pathogenicity. Here we describe the genetic characterization of a novel putative dISFV, termed Guapiaçu virus (GUAPV). Distinct strains of GUAPV were isolated from pools of Aedes terrens and Aedes scapularis mosquitoes. Additionally, we also detected viral GUAPV RNA in a plasma sample of an individual febrile from the Amazon region (North of Brazil). Although GUAPV did not replicate in tested mammalian cells, 3'UTR secondary structures duplication and codon usage index were similar to pathogenic flavivirus.
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http://dx.doi.org/10.1038/s41598-021-83879-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907106PMC
February 2021

Norovirus strains in patients with acute gastroenteritis in rural and low-income urban areas in northern Brazil.

Arch Virol 2021 Mar 19;166(3):905-913. Epub 2021 Jan 19.

Enteric Diseases Laboratory, Virology Center, Adolfo Lutz Institute, Av. Dr Arnaldo, nº 355, São Paulo, SP, 01246-902, Brazil.

From 2010-2016, a total of 251 stool samples were screened for norovirus using next-generation sequencing (NGS) followed by phylogenetic analysis to investigate the genotypic diversity of noroviruses in rural and low-income urban areas in northern Brazil. Norovirus infection was detected in 19.9% (50/251) of the samples. Eight different genotypes were identified: GII.4_Sydney[P31] (64%, 32/50), GII.6[P7] (14%, 7/50), GII.17[P17] (6%, 3/50), GII.1[P33] (6%, 3/50), GII.3[P16] (4%, 2/50), GII.2[P16] (2%, 1/50), GII.2[P2] (2%, 1/50), and GII.4_New Orleans[P4] (2%, 1/50). Distinct GII.6[P7] variants were recognized, indicating the presence of different co-circulating strains. Elucidating norovirus genetic diversity will improve our understanding of their potential health burden, in particular for the GII.4_Sydney[P31] variant.
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http://dx.doi.org/10.1007/s00705-020-04944-5DOI Listing
March 2021

New Approaches for the Treatment of Chagas Disease.

Curr Drug Targets 2021 ;22(7):835-841

Laboratorio de Imunologia, Instituto do Coracao, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.

Chagas disease, caused by the protozoan Trypanosoma cruzi is a neglected tropical disease with high prevalence (5.7 million in Latin America, WHO 2015), significant burden, and significant morbimortality mostly due to severe heart disorders during the chronic phase of infection. Chagas disease is endemic in Latin America, and medical care for the disease is the major expense for Brazil's Universal Healthcare System (Sistema Único de Saúde (SUS). The efficacy of the available drugs benznidazole and nifurtimox are low for the chronic phase of Chagas disease, the phase in which most patients are diagnosed, and there are frequent side effects, and drug resistance occurs. The rapid deployment of new drug regimens that are effective for the chronic phase treatment is low-cost and less toxic than the currently available therapy, which is a global priority. Repurposing drugs already in clinical use with other combinations would be the fastest and safest strategy for treating Chagas disease patients. We hypothesize that the combined treatment using repurposing drugs with benznidazole will be more efficacious than benznidazole alone. This needs to be tested further both in vitro and in animal models to understand the efficacy of the treatment before performing human clinical trials. We further hypothesize that producing nanoparticle formulation of the drugs can reduce their toxicity and improve therapeutic use.
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http://dx.doi.org/10.2174/1389450121999201124122643DOI Listing
January 2021

Development of potential proteasome inhibitors against .

J Biomol Struct Dyn 2020 Oct 19:1-15. Epub 2020 Oct 19.

Centre for Drug Design Discovery and Development (C4D), SRM University, Delhi, Haryana, India.

Tuberculosis (TB) has been recently declared as a health emergency because of sporadic increase in Multidrug-resistant Tuberculosis (MDR-TB) problem throughout the world. TB causing bacteria, has become resistant to the first line of treatment along with second line of treatment and drugs, which are accessible to us. Thus, there is an urgent need of identification of key targets and development of potential therapeutic approach(s), which can overcome the complications. In the present study, proteasome has been taken as a potential target as it is one of the key regulatory proteins in propagation. Further, a library of 400 compounds (small molecule) from Medicines for Malaria Venture (MMV) were screened against the target (proteasome) using molecular docking and simulation approach, and selected lead compounds were validated in model. In this study, we have identified two potent small molecules from the MMV Pathogen Box library, MMV019838 and MMV687146 with -9.8kcal/mol and -8.7kcal/mol binding energy respectively, which actively interact with the catalytic domain/active domain of proteasome and inhibit the growth in culture. Furthermore, the molecular docking and simulation study of MMV019838 and MMV687146 with proteasome show strong and stable interaction with compared to human proteasome and show no cytotoxicity effect. A better understanding of proteasome inhibition in in and model would eventually allow us to understand the molecular mechanism(s) and discover a novel and potent therapeutic agent against Tuberculosis. Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. Efflux pump activity was tested for a specific compound MMV019838 which was showing good in silico results than MIC values.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1835722DOI Listing
October 2020

Shorter telomere length, higher telomerase activity in association with tankyrase gene polymorphism contribute to high-altitude pulmonary edema.

Hum Mol Genet 2020 11;29(18):3094-3106

Department of Biotechnology, SRM University, Delhi-NCR, Sonepat, Haryana 131029, India.

High-altitude pulmonary edema (HAPE) is a noncardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs. We hence investigated the association of TNKS and telomeres with HAPE to delineate their potential role at HA. The study was performed in three groups, High-altitude pulmonary edema patients (HAPE-p, n = 200), HAPE-resistant sojourners (HAPE-r, n = 200) and highland permanent healthy residents (HLs, n = 200). Variants of TNKS were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Plasma TNKS level was estimated using enzyme-linked immunosorbent assay, expression of TNKS and relative telomere length were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and telomerase activity was assessed by the telomere repeat amplification protocol assay. TNKS poly-ADP ribosylates the telomere-repeat factor (TRF), which is a negative regulator of telomere length. Consequently, TRF expression was also measured by RT-qPCR. The TNKS heterozygotes rs7015700GA were prevalent in HLs compared to the HAPE-p and HAPE-r. The plasma TNKS was significantly decreased in HAPE-p than HAPE-r (P = 0.006). TNKS was upregulated 9.27 folds in HAPE-p (P = 1.01E-06) and downregulated in HLs by 3.3 folds (P = 0.02). The telomere length was shorter in HAPE-p compared to HAPE-r (P = 0.03) and HLs (P = 4.25E-4). The telomerase activity was significantly higher in HAPE-p compared to both HAPE-r (P = 0.01) and HLs (P = 0.001). HAPE-p had the lowest TNKS levels (0.186 ± 0.031 ng/μl) and the highest telomerase activity (0.0268 amoles/μl). The findings of the study indicate the association of TNKS and telomeres with HA adaptation/maladaptation.
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http://dx.doi.org/10.1093/hmg/ddaa205DOI Listing
November 2020

Use Chou's 5-steps rule to evaluate protective efficacy induced by antigenic proteins of Mycobacterium tuberculosis encapsulated in chitosan nanoparticles.

Life Sci 2020 Sep 11;256:117961. Epub 2020 Jun 11.

Institute of Biological Sciences, Federal University of Para, Para 66075-000, Brazil. Electronic address:

The study focuses on whether antigenic proteins encapsulated in biopolymeric nanoparticles can augment protective efficacy. Chitosan nanoparticles (ChN) were prepared by ionic gelation method and Culture Filtrate Proteins (CFP) - CFP-10 and CFP-21 of Mycobacterium tuberculosis (Mtb) were encapsulated in ChN. The binding efficiency of nanoparticles with CFP-10 and CFP-21 proteins was confirmed by UV-Spectrophotometer. The efficacy of nanoparticles-encapsulated antigenic proteins administered intraperitoneal against Mtb aerosol infection was evaluated in Balb/c mice. Protection study was done by bacterial counts [CFU]. CFP-10 and CFP-21 proteins primed cells demonstrated a Th1 bias T cell response in an ex vivo assay. ChN-CFP10 and ChN-CFP21 nanoparticles have both protective and therapeutic potential against Mtb. In the group of mice immunized with CHN-CFP-10 the number of colonies reduced significantly from day 15 to day 60. ChN-CFP-21 showed maximum protection in ChN-CFP-21 immunized mice. ChN-CFP-10 and ChN-CFP-21 clearly showed enhanced protection against Mtb.
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http://dx.doi.org/10.1016/j.lfs.2020.117961DOI Listing
September 2020

First identification of mammalian orthoreovirus type 3 by gut virome analysis in diarrheic child in Brazil.

Sci Rep 2019 12 9;9(1):18599. Epub 2019 Dec 9.

Institute of Biological Sciences, Federal University of Para, Para, 66075-000, Brazil.

Diarrhea remains one of the most common causes of deaths in children. Although many studies have investigated the prevalence of enteric pathogens around the globe some diarrheal episodes remain unexplained. It is possible that some yet-unidentified viral agents could be related to these cases of gastroenteritis. By using viral metagenomics techniques, we screened 251 fecal samples of children between 0.5 to 2.5-year-old with acute diarrhea not associated with common pathogens. These children live in rural areas and have different levels of contact with animals such as pigs, cows and bats. Here we report a complete genome of one mammalian orthoreovirus (MRV) type 3, denoted TO-151/BR, detected in a female child in the state of Tocantins (north of Brazil). Brazilian TO-151/BR strain was classified as MRV-3 based on S1 phylogeny and was closely related to porcine Asian strains. Phylogenetic analyses showed that other segments were more similar to MRV-3s of different geographic locations and hosts, including human and bats, highlighting genome reassortment and lack of host-specific barriers. This is the first report of MRV-3 in South America and a hypothesis of a silent long-term circulation of this virus in Brazil has been raised.
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http://dx.doi.org/10.1038/s41598-019-55216-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901473PMC
December 2019

Disease Tolerance and Pathogen Resistance Genes May Underlie Persistence and Differential Progression to Chagas Disease Cardiomyopathy.

Front Immunol 2018 3;9:2791. Epub 2018 Dec 3.

Laboratorio de Imunologia, Instituto do Coracao, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil.

Chagas disease is caused by infection with the protozoan and affects over 8 million people worldwide. In spite of a powerful innate and adaptive immune response in acute infection, the parasite evades eradication, leading to a chronic persistent infection with low parasitism. Chronically infected subjects display differential patterns of disease progression. While 30% develop chronic Chagas disease cardiomyopathy (CCC)-a severe inflammatory dilated cardiomyopathy-decades after infection, 60% of the patients remain disease-free, in the asymptomatic/indeterminate (ASY) form, and 10% develop gastrointestinal disease. Infection of genetically deficient mice provided a map of genes relevant for resistance to infection, leading to the identification of multiple genes linked to survival to infection. These include pathogen resistance genes (PRG) needed for intracellular parasite destruction, and genes involved in disease tolerance (protection against tissue damage and acute phase death-DTG). All identified DTGs were found to directly or indirectly inhibit IFN-γ production or Th1 differentiation. We hypothesize that the absolute need for DTG to control potentially lethal IFN-γ PRG activity leads to persistence and establishment of chronic infection. IFN-γ production is higher in CCC than ASY patients, and is the most highly expressed cytokine in CCC hearts. Key DTGs that downmodulate IFN-γ, like IL-10, and Ebi3/IL27p28, are higher in ASY patients. Polymorphisms in PRG and DTG are associated with differential disease progression. We thus hypothesize that ASY patients are disease tolerant, while an imbalance of DTG and IFN-γ PRG activity leads to the inflammatory heart damage of CCC.
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http://dx.doi.org/10.3389/fimmu.2018.02791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286977PMC
October 2019

Vimentin and Anti Vimentin Antibodies in Chagas' Disease.

Arq Bras Cardiol 2018 Apr 12;110(4):348-353. Epub 2018 Mar 12.

Universidade de São Paulo (USP), São Paulo, SP - Brazil.

Background: Vimentin is a main structural protein of the cell, a component of intermediate cell filaments and immersed in cytoplasm. Vimentin is mimicked by some bacterial proteins and anti-vimentin antibodies occur in autoimmune cardiac disease, as rheumatic fever. In this work we studied vimentin distribution on LLC-MK2 cells infected with T. cruzi and anti-vimentin antibodies in sera from several clinical pictures of Chagas' disease or American Trypanosomiasis, in order to elucidate any vimentin involvement in the humoral response of this pathology.

Objective: We standardized an indirect immunofluorescence assay (IFI) to determine sub cellular expression in either parasites and host cells, and ELISA to evaluate anti-vimentin antibodies in sera fron chagasic patients.

Methods: We analyzed the distribution of vimentin in culture cells using indirect fluorescent assays, using as external controls anti-T. cruzi sera, derived from chronic infected patients for identification of the parasites in the same model. After infection and growth of T.cruzi amastigotes, those cells express larger amounts of vimentin, with heavy staining of cytoplasm outside the parasitophorous vacuole and some particle shadowing patterns, suggesting that vimentin are associated with cell cytoplasm. Anti-vimentin antibodies were present in most American trypanosomiasis samples, but notably, they are much more present in acute (76, 9%) or clinical defined syndromes, especially cardiac disease (87, 9%). Paradoxically, they were relatively infrequent in asymptomatic (25%) infected patients, which had a clearly positive serological reaction to parasite antigens, but had low frequency of anti-vimentin antibodies, similar to controls (2,5%).

Conclusion: Our current data revealed that anti-vimentin antibodies induced during T. cruzi infection could be a marker of active disease in the host and its levels could also justify drug therapy in American Trypanosomiasis chronic infection, as a large group of asymptomatic patients would be submitted to treatment with frequent adverse reactions of the available drugs. Anti-vimentin antibodies could be a marker of cardiac muscle cell damage, appearing in American Trypanosomiasis patients during active muscle cell damage.
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http://dx.doi.org/10.5935/abc.20180038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941957PMC
April 2018

Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection.

Sci Rep 2017 12 21;7(1):17990. Epub 2017 Dec 21.

Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.

Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions. Mouse models of T. cruzi infection have been used to study heart damage in Chagas disease. The aim of this study was to provide an interactome between miRNAs and their targetome in Chagas heart disease by integrating gene and microRNA expression profiling data from hearts of T. cruzi infected mice. Gene expression profiling revealed enrichment in biological processes and pathways associated with immune response and metabolism. Pathways, functional and upstream regulator analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs revealed enrichment in biological processes and pathways such as IFNγ, TNFα, NF-kB signaling signatures, CTL-mediated apoptosis, mitochondrial dysfunction, and Nrf2-modulated antioxidative responses. We also observed enrichment in other key heart disease-related processes like myocarditis, fibrosis, hypertrophy and arrhythmia. Our correlation study suggests that miRNAs may be implicated in the pathophysiological processes taking place the hearts of acutely T. cruzi-infected mice.
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http://dx.doi.org/10.1038/s41598-017-18080-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740174PMC
December 2017

Transcription factor Foxo1 is essential for IL-9 induction in T helper cells.

Nat Commun 2017 10 9;8(1):815. Epub 2017 Oct 9.

Center for Human Microbial Ecology, Translational Health Science & Technology Institute, NCR Biotech Science Cluster, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad, Haryana, 121 001, India.

Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3 regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1. Mechanistically, Foxo1 binds and transactivates IL-9 and IRF4 promoters in Th9, Th17 and iTreg cells. Furthermore, loss of Foxo1 attenuates IL-9 in mouse and human Th9 and Th17 cells, and ameliorates allergic inflammation in asthma. Our findings thus identify that Foxo1 is essential for IL-9 induction in Th9 and Th17 cells.The transcription factor Foxo1 can control regulatory T cell and Th1 function. Here the authors show that Foxo1 is also critical for IL-9 production by Th9 cells and other IL-9-producing cells.
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http://dx.doi.org/10.1038/s41467-017-00674-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634439PMC
October 2017

Glycoxidation of biological macromolecules: a critical approach to halt the menace of glycation.

Glycobiology 2014 Nov 19;24(11):979-90. Epub 2014 Jun 19.

Department of Biochemistry, Central Drug Research Institute, Lucknow, India

Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.
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http://dx.doi.org/10.1093/glycob/cwu057DOI Listing
November 2014

Structural and functional studies on Ribonuclease S, retro S and retro-inverso S peptides.

Biochem Biophys Res Commun 2007 Dec 18;364(3):608-13. Epub 2007 Oct 18.

Tata Institute of Fundamental Research, Colaba, Mumbai 400005, India.

Ribonuclease S peptide and S protein offer a unique complementation system to understand the finer features of molecular recognition. In the present study the S peptide (1-16), and its retro and retro-inverso analogs have been analyzed for their structural and biological attributes. RPHPLC, CD, and NMR analyses have revealed that the physicochemical and conformational properties of the S peptide are distinct from those of its retro and retro-inverso analogs. On the functional side, while the S peptide complemented the S protein to give RNase activity, was recognized by anti-S peptide antibodies and induced T cell proliferation, neither the retro nor the retro-inverso S peptides could do so.
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http://dx.doi.org/10.1016/j.bbrc.2007.10.056DOI Listing
December 2007