A5088542908- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Protein Interaction Studies and Fluorescence Analysis
- Enzyme Structure and Function
- Analytical Chemistry and Chromatography
- thermodynamics and calorimetric analyses
- Protein purification and stability
- Bacterial Genetics and Biotechnology
- Antibiotics Pharmacokinetics and Efficacy
- Biochemical and Molecular Research
- Molecular spectroscopy and chirality
- Metal complexes synthesis and properties
- Mycotoxins in Agriculture and Food
- Alzheimer's disease research and treatments
- Spectroscopy and Chemometric Analyses
- Drug Transport and Resistance Mechanisms
- Advanced Chemical Sensor Technologies
- Lipoproteins and Cardiovascular Health
- Porphyrin Metabolism and Disorders
- Liquid Crystal Research Advancements
- Prion Diseases and Protein Misfolding
- Silk-based biomaterials and applications
- Research on Leishmaniasis Studies
- Renin-Angiotensin System Studies
Neogen (United States)
2010-2024
Queen's University Belfast
2020
Pfizer (United States)
2005-2010
Nerviano Medical Sciences
2003
Pharmac
2003
W.E. Upjohn Institute for Employment Research
1991-1999
Competition ligand-based NMR screening experiments have recently been introduced to overcome most of the problems associated with traditional screening. Molecules marginal solubility and high affinity for a given target can be easily identified in high-throughput manner by chemical mixtures against presence weak- medium-affinity ligand known binding constant. While original competition-based approaches utilized (1)H detection, significant advantages are obtained using (19)F detection. The...
Abstract Dihydrofolate reductase (DHFR) is the enzyme responsible for NADPH‐dependent reduction of 5,6‐dihydrofolate to 5,6,7,8‐tetrahydrofolate, an essential cofactor in synthesis purines, thymidylate, methionine, and other key metabolites. Because its importance multiple cellular functions, DHFR has been subject much research targeting with anticancer, antibacterial, antimicrobial agents. Clinically used compounds include methotrexate treatment cancer diaminopyrimidines (DAPs) such as...
Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2-7% of patients may experience statin-induced myalgia limits compliance a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors improved HMGR affinity therapeutic index relative myalgia. These...
Phosphopantetheine adenylyltransferase (PPAT) from Escherichia coli is an essential hexameric enzyme that catalyzes the penultimate step in coenzyme A (CoA) biosynthesis and a target for antibacterial drug discovery. The utilizes Mg-ATP phosphopantetheine (PhP) to generate dephospho-CoA (dPCoA) pyrophosphate. When overexpressed E. coli, PPAT copurifies with tightly bound CoA, suggesting feedback inhibitory role this cofactor. Using enzyme-coupled assay forward-direction reaction...
The amyloid peptide (Aβ), derived from the proteolytic cleavage of precursor protein (APP) by β- and γ-secretases, undergoes multistage assemblies to fibrillar depositions in Alzheimer's brains. Aβ protofibrils were previously identified as an intermediate preceding insoluble fibrils. While characterizing a synthetic variant named EV40 that has mutations first two amino acids (D1E/A2V), we discerned unusual aggregation profiles this variant. In comparison fibrillogenesis cellular toxicity...
High-throughput screening is utilized by pharmaceutical researchers and, increasingly, academic investigators to identify agents that act upon enzymes, receptors, and cellular processes. Screening hits include molecules specifically bind the target a greater number of non-specific compounds. It necessary 'triage' these subset worthy further exploration. As part our antibacterial drug discovery effort, we applied suite biochemical biophysical tools accelerate triage process. We describe...
In this study, we formulate a computational reaction model following chemical kinetic theory approach to predict the binding rate constant for siRNA-RISC complex formation reaction. The allowed us study potency difference between 2-nt 3' overhangs against blunt-ended siRNA molecules in an RNA interference (RNAi) system. predicted by was fed into stochastic simulation of RNAi system (using Gillespie simulator) overall effect. We observed that stochasticity transcription/translation machinery...
We used a temperature-jump isothermal denaturation procedure with various methods of detection to evaluate the quality putative inhibitors MurB discovered by high-throughput screening. Three optical detection-ultraviolet hyperchromicity absorbance, fluorescence bound dyes, and circular dichroism-as well as differential scanning calorimetry were dissect effects two chemical compounds natural substrate on enzyme. The kinetics process binding detected quenching flavin quantitate dose...