A5057213428- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Reproductive System and Pregnancy
- Metabolism, Diabetes, and Cancer
- Reproductive Health and Contraception
- Neuropeptides and Animal Physiology
- Oral microbiology and periodontitis research
- Diet, Metabolism, and Disease
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Anesthesia and Pain Management
- Reproductive Physiology in Livestock
- Peroxisome Proliferator-Activated Receptors
- Antifungal resistance and susceptibility
- Nicotinic Acetylcholine Receptors Study
- Indoor Air Quality and Microbial Exposure
- Pain Mechanisms and Treatments
- Synthesis and biological activity
- Global Cancer Incidence and Screening
- Monoclonal and Polyclonal Antibodies Research
- Probiotics and Fermented Foods
- Pregnancy and Medication Impact
- Reproductive Biology and Fertility
- Adipose Tissue and Metabolism
- Synthesis and Reactivity of Heterocycles
George Eliot Hospital NHS Trust
2024
George Eliot Hospital
2024
Bradford Royal Infirmary
2024
Leeds Teaching Hospitals NHS Trust
2024
The Ohio State University
2022
Janssen (United States)
2012-2020
Springhouse
2016
Janssen (Belgium)
2006-2015
Johnson & Johnson (United States)
2005-2012
University of Manchester
1987-2010
The performance of several commercially available docking programs is compared in the context virtual screening. Five different protein targets are used, each with known ligands. simulated screening deck comprised 1000 molecules from a cleansed version MDL drug data report and 49 For many ligands, crystal structures relevant protein−ligand complexes were available. We attempted to run experiments method that as similar possible. given method, hit rates improved versus what would be expected...
SUMMARY: Fibrillar and fimbriate strains of Streptococcus salivarius were compared for their ability to adhere buccal epithelial cells saliva-coated hydroxyapatite beads, coaggregate with Veillonella strains. The fibrillar Lancefield group K adhered statistically significantly better both beads than the strains, which lacked antigen. After 1 h coaggregated V. parvula strain VI, but after 24 h, coaggregation reached approximately 90%. Freshly isolated all S. percentage varied considerably...
Abstract Pain places a devastating burden on patients and society current pain therapeutics exhibit limitations in efficacy, unwanted side effects the potential for drug abuse diversion. Although genetic evidence has clearly demonstrated that voltage-gated sodium channel, Nav1.7, is critical to sensation mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated dramatic analgesia observed Nav1.7-null subjects. Using tarantula venom-peptide ProTX-II as scaffold, we...
The multidrug resistant (MDR) transporter P-glycoprotein (P-gp) is constitutively expressed in normal tissues, where its spatial distribution defines it as an important element reducing the systemic exposure and tissue access of potentially harmful xenobiotics. We sought to determine whether P-gp functionally within alveolar epithelium lung, particular predominant cell type this barrier, epithelial (AE) I cell. By immunohistochemistry, MDR-1/mdr-1 was localized luminal membranes AE human rat...
The necessity to generate conformations that sample the entire conformational space accessible a given molecule is ubiquitous in field of computer-aided drug design. Protein−ligand docking, 3D database searching, and QSAR are three commonly used techniques depend critically upon quality diversity generated conformers. Although there wide range search algorithms available, extent which they often unclear. To address this question, we conducted robust comparison implemented several widely...
Voltage-gated sodium channels (VGSCs) are essential to the normal function of vertebrate nervous system. Aberrant VGSCs underlies a variety disorders, including epilepsy, arrhythmia, and pain. A large number animal toxins target these ion may have significant therapeutic potential. Most toxins, however, not been characterized in detail. Here, by combining patch clamp electrophysiology radioligand binding studies with peptide mutagenesis, NMR structure determination, molecular modeling, we...
A number of classes proteins have been engineered for high stability using consensus sequence design methods. Here we describe the engineering a novel albumin binding domain (ABD) three-helix bundle protein. The resulting ABD molecule, called ABDCon, is expressed at levels in soluble fraction Escherichia coli and highly stable, with melting temperature 81.5°C. ABDCon binds human, monkey mouse serum albumins affinity as 61 pM. solution structure consistent epitope mapping studies enabled...
The structural determinants of type II' β-turns were probed through a comprehensive CD, NMR, and molecular dynamics analysis 10 specially designed β-hairpin peptides. peptide model used in this study is synthetic, water-soluble, 14-residue cyclic analogue gramicidin S which contains two well-defined connected by highly stable, amphipathic, antiparallel β-sheet. A variety coded noncoded amino acids systematically substituted one the turns to analyze effects backbone chirality, side-chain...
Carnobacteriocin B2 (CbnB2), a type IIa bacteriocin, is 48 residue antimicrobial peptide from the lactic acid bacterium Carnobacterium pisicola LV17B. Type bacteriocins have conserved YGNGVXC sequence near N-terminus and usually contain disulfide bridge. CbnB2 seemed to be unique in that its two cysteines (Cys9 Cys14) could isolated as free thiols [Quadri et al. (1994) J. Biol. Chem. 26, 12204−12211]. To establish structural consequences of presence or absence bridge investigate if...
Propranolol was introduced as a 0-adrenergic receptor antagonist, having about ten times the potency of pronethalol against isoprenaline (Black, Crowther, Shanks, Smith, and Dornhorst, I964) while being devoid intrinsic sympathomimetic activity.A preliminary investigation with systemic racemic propranolol intravenously by mouth showed that it caused lowering ocular tension in patients glaucoma (Phillips, Howitt, Rowlands, I967).These observations were confirmed Cote Drance (i968) using...
Serum zinc was measured by atomic absorption spectrophotometry in sixty-five children with atopic eczema and seventy-nine control children. The mean serum of the patients, (11.4 +/- 2.0 mumol/l) significantly lower than that controls (13.7 2.3 mumol/l, P less 0.0001). There no significant correlation between patients' concentration either height/weight centile or a subjective assessment severity extent eczema. Of eleven patients below 10 six had recurrent infections skin, greater proportion...
Dengue virus poses a significant global health threat as the source of increasingly deleterious dengue fever, hemorrhagic and shock syndrome. As no specific antiviral treatment exists for infection, considerable effort is being applied to discover therapies drugs maintenance prevention these afflictions. The primarily transmitted by mosquitoes, infection occurs following viral endocytosis host cells. Upon entering cell, RNA translated into large multisubunit polyprotein which...
A fragment-based drug design paradigm has been successfully applied in the discovery of lead series ketohexokinase inhibitors. The consists three iterations design, synthesis, and X-ray crystallographic screening to progress low molecular weight fragments leadlike compounds. Applying electron density within protein binding site as defined by crystallography, one can generate target specific leads without use affinity data. Our approach contrasts with most methodology where solution activity...
Attenuation of fructose metabolism by the inhibition ketohexokinase (KHK; fructokinase) should reduce body weight, free fatty acids, and triglycerides, thereby offering a novel approach to treat diabetes obesity in response modern diets. We have identified potent, selective inhibitors human hepatic KHK within series pyrimidinopyrimidines (1). For example, 8, 38, 47 exhibited IC50 values 12, 7, 8 nM, respectively, also showed potent cellular (IC50 < 500 nM), which relates their intrinsic...
Journal Article Serum levels of trace metals in children with atopic eczema Get access T.J. DAVID, DAVID Department Child Health, University Manchester, U.K. Dr T.J.David, Booth Hall Children's Hospital, Charlestown Road, Blackley, Manchester M9 2AA, Search for other works by this author on: Oxford Academic Google Scholar F.E. WELLS, WELLS Chemical Pathology, T.C. SHARPE, SHARPE Faculty Medicine Computational Group, A.C.C. GIBBS, GIBBS Community Medicine, J. DEVLIN British Dermatology,...
Cardiovascular disease is the most common cause of morbidity and mortality in developed nations. To effectively target dyslipidemia to reduce risk cardiovascular disease, it may be beneficial activate peroxisome proliferator-activated receptors (PPARs) PPARα PPARδ simultaneously through a single molecule. Replacement methylthiazole 5 (the selective agonist) with [1,2,4]thiadiazole gave compound 13, which unexpectedly displayed submicromolar potency as partial agonist at addition high PPARδ....
We report on the structural comparison of corporate collections Johnson & Pharmaceutical Research Development (JNJPRD) and 3-Dimensional Pharmaceuticals (3DP), performed in context recent acquisition 3DP by JNJPRD. The main objective study was to assess druglikeness library extent which it enriched chemical diversity JNJPRD collection. two databases, at time acquisition, collectively contained more than 1.1 million compounds with a clearly defined description. analysis based clustering...
With the goal of identifying a CETP inhibitor with high in vitro potency and optimal vivo efficacy, conformationally constrained molecule was designed based on highly potent flexible 13. The synthetic chemistry efforts led to discovery selective 12. In high-fat fed hamsters, human transgenic mice, cynomolgus monkeys, efficacy 12 for raising HDL-C demonstrated be comparable torcetrapib.
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTAnalogues of Bacteriocins: Antimicrobial Specificity and Interactions Leucocin A with Its Enantiomer, Carnobacteriocin B2, Truncated DerivativesLiang Z. Yan, Alan C. Gibbs, Michael E. Stiles, David S. Wishart, John VederasView Author Information Department Chemistry, Faculty Pharmacy Pharmaceutical Sciences, Agricultural, Food Nutritional Science, University Alberta, Edmonton, Alberta T6G 2G2, Canada Cite this: J. Med. Chem. 2000, 43, 24,...