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Your search keyword '"Vipulkumar K. Patel"' showing total 12 results
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12 results on '"Vipulkumar K. Patel"'

1. Differential recognition of HIV-stimulated IL-1β and IL-18 secretion through NLR and NAIP signalling in monocyte-derived macrophages.

Author

Kathy Triantafilou, Christopher J K Ward, Magdalena Czubala, Robert G Ferris, Emma Koppe, Curt Haffner, Vincent Piguet, Vipulkumar K Patel, Heather Amrine-Madsen, Louise K Modis, Seth L Masters, and Martha Triantafilou

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Macrophages are important drivers of pathogenesis and progression to AIDS in HIV infection. The virus in the later phases of the infection is often predominantly macrophage-tropic and this tropism contributes to a chronic inflammatory and immune activation state that is observed in HIV patients. Pattern recognition receptors of the innate immune system are the key molecules that recognise HIV and mount the inflammatory responses in macrophages. The innate immune response against HIV-1 is potent and elicits caspase-1-dependent pro-inflammatory cytokine production of IL-1β and IL-18. Although, NLRP3 has been reported as an inflammasome sensor dictating this response little is known about the pattern recognition receptors that trigger the "priming" signal for inflammasome activation, the NLRs involved or the HIV components that trigger the response. Using a combination of siRNA knockdowns in monocyte derived macrophages (MDMs) of different TLRs and NLRs as well as chemical inhibition, it was demonstrated that HIV Vpu could trigger inflammasome activation via TLR4/NLRP3 leading to IL-1β/IL-18 secretion. The priming signal is triggered via TLR4, whereas the activation signal is triggered by direct effects on Kv1.3 channels, causing K+ efflux. In contrast, HIV gp41 could trigger IL-18 production via NAIP/NLRC4, independently of priming, as a one-step inflammasome activation. NAIP binds directly to the cytoplasmic tail of HIV envelope protein gp41 and represents the first non-bacterial ligand for the NAIP/NLRC4 inflammasome. These divergent pathways represent novel targets to resolve specific inflammatory pathologies associated with HIV-1 infection in macrophages.

Published
2021
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2. Identification and Optimization of a Ligand-Efficient Benzoazepinone Bromodomain and Extra Terminal (BET) Family Acetyl-Lysine Mimetic into the Oral Candidate Quality Molecule I-BET432

Author

Philip G. Humphreys, Niall A. Anderson, Paul Bamborough, Andrew Baxter, Chun-wa Chung, Rosa Cookson, Peter D. Craggs, Toryn Dalton, Julie C. L. Fournier, Laurie J. Gordon, Heather F. Gray, Matthew W. Gray, Richard Gregory, David J. Hirst, Craig Jamieson, Katherine L. Jones, Hripsimee Kessedjian, David Lugo, Grant McGonagle, Vipulkumar K. Patel, Christopher Patten, Darren L. Poole, Rab K. Prinjha, Cesar Ramirez-Molina, Inmaculada Rioja, Gail Seal, Kayleigh A. J. Stafford, Rishi R. Shah, Daniel Tape, Natalie H. Theodoulou, Laura Tomlinson, Sabri Ukuser, Ian D. Wall, Natalie Wellaway, and Gemma White

Subjects
Histones, Protein Domains, Lysine, Drug Discovery, Humans, Molecular Medicine, Ligands, Transcription Factors
Abstract

The bromodomain and extra terminal (BET) family of proteins are an integral part of human epigenome regulation, the dysregulation of which is implicated in multiple oncology and inflammatory diseases. Disrupting the BET family bromodomain acetyl-lysine (KAc) histone protein-protein interaction with small-molecule KAc mimetics has proven to be a disease-relevant mechanism of action, and multiple molecules are currently undergoing oncology clinical trials. This work describes an efficiency analysis of published GSK pan-BET bromodomain inhibitors, which drove a strategic choice to focus on the identification of a ligand-efficient KAc mimetic with the hypothesis that lipophilic efficiency could be drastically improved during optimization. This focus drove the discovery of the highly ligand-efficient and structurally distinct benzoazepinone KAc mimetic. Following crystallography to identify suitable growth vectors, the benzoazepinone core was optimized through an explore-exploit structure-activity relationship (SAR) approach while carefully monitoring lipophilic efficiency to deliver I-BET432 (

Published
2022

5. Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA

Author

Alison J-A, Woolford, Philip J, Day, Véronique, Bénéton, Valerio, Berdini, Joseph E, Coyle, Yann, Dudit, Pascal, Grondin, Pascal, Huet, Lydia Y W, Lee, Eric S, Manas, Rachel L, McMenamin, Christopher W, Murray, Lee W, Page, Vipulkumar K, Patel, Florent, Potvain, Sharna J, Rich, Yingxia, Sang, Don O, Somers, Lionel, Trottet, Zehong, Wan, and Xiaomin, Zhang

Subjects
Models, Molecular, Dose-Response Relationship, Drug, Lactams, Molecular Structure, Administration, Oral, Biological Availability, Crystallography, X-Ray, Rats, Structure-Activity Relationship, Dogs, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Animals, Humans, Tissue Distribution, Enzyme Inhibitors
Abstract

Lp-PLA

Published
2016

6. Stereospecific synthesis of chlamydocin

Author

Vipulkumar K. Patel, Christopher R. A. Godfrey, Jack E. Baldwin, and R. M. Adlington

Subjects
chemistry.chemical_classification, Tetrapeptide, Stereochemistry, Organic Chemistry, Free-radical reaction, Epoxide, Biochemistry, Cyclic peptide, chemistry.chemical_compound, Chemical coupling, Stereospecificity, chemistry, Chlamydocin, Drug Discovery, Peptide synthesis, Organic chemistry
Abstract

A stereospecific synthesis of the cyclic tetrapeptide chlamydocin via free radical homologation from a ( S )-2-amino-5-iodopentanoic acid containing cyclic tetrapeptide is described.

Published
1993

7. ChemInform Abstract: Stereospecific Synthesis of Chlamydocin

Author

Vipulkumar K. Patel, R. M. Adlington, Christopher R. A. Godfrey, and Jack E. Baldwin

Subjects
chemistry.chemical_classification, Stereospecificity, Chlamydocin, Tetrapeptide, Stereochemistry, Chemistry, General Medicine, Amino acid
Abstract

A stereospecific synthesis of the cyclic tetrapeptide chlamydocin via free radical homologation from a ( S )-2-amino-5-iodopentanoic acid containing cyclic tetrapeptide is described.

Published
2010

8. HIV in Gujarat: An Exploration of Religious Coping Strategies and Quality of Life

Author

Jiten Chaudhary, Vipulkumar K Patel, William C. Mathews, Paresh Chandegara, Alap J Mehta, Kartavya J. Vyas, and Gulab R Patel

Subjects
Aids patients, medicine.medical_specialty, Coping (psychology), Health professionals, Patient interviews, Public Health, Environmental and Occupational Health, Psychological intervention, Alternative medicine, Human immunodeficiency virus (HIV), medicine.disease_cause, medicine, Sociology, Psychiatry, Clinical psychology
Abstract

The present study investigated the relationships between religious coping strategies (positive and negative) and six quality of life domains (physical, psychological, independence, social, environment, and spiritual) in 160 HIV-infected patients in Gujarat, India. Data were collected from patient interviews at a public, university-based hospital in Surat. Participants with lower annual incomes used religious coping more often (≤0.01). Positive religious coping subscribers (34.4%) were more likely to have been infected recently (OR, 3.07; 95% CI, 1.19–7.95). After controlling for associated variables, all religious coping strategies were associated with a better quality of life in the following domains: physical, psychological, independence and environment (p 0.05). These results have implications for designing future religious coping interventions and for helping healthcare professionals assess religious coping in HIV/AIDS patients.

Published
2014

10. A new homolytic method for the stereospecific synthesis of (2S,9S)-2-amino-8-oxo-9,10-epoxydecanoic acid in protected form

Author

Vipulkumar K. Patel, Jack E. Baldwin, Christopher R. A. Godfrey, and Robert M. Adlington

Subjects
chemistry.chemical_classification, Ketone, Stereospecificity, chemistry, Tetrapeptide, Stereochemistry, Molecular Medicine, Homolysis
Abstract

(2S,9S)-2-Amino-8-oxo-9,10-epoxydecanoic acid 1, (AOE), has been synthesized in protected form by homolytic homologation from protected (S)-2-amino-5-iodopentanoic acid.

Published
1991

11. ChemInform Abstract: Desulfurization of Penicillins with Triphenylstannane

Author

L. G. King, Vipulkumar K. Patel, Jack E. Baldwin, Robert M. Adlington, and Tae Won Kang

Subjects
medicine.drug_class, Chemistry, Cephalosporin, polycyclic compounds, medicine, Organic chemistry, General Medicine, biochemical phenomena, metabolism, and nutrition, Triphenylstannane, Flue-gas desulfurization
Abstract

Treatment of the penicillins (I) and the cephalosporin (III) with triphenylstannane results in desulfurization, forming the β-lactams (II) and (IV).

Published
1989

12. Desulfhurisation of Penicillins with Triphenylstannane

Author

Jack E. Baldwin, Robert M. Adlington, Tae Won Kang, Lionel G. King, and Vipulkumar K. Patel

Subjects
Pharmacology, Reaction mechanism, chemistry.chemical_compound, Bicyclic molecule, Chemistry, Organic Chemistry, Lactam, Free-radical reaction, Combinatorial chemistry, Analytical Chemistry, Triphenylstannane
Published
1989

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