A5033034035- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Coordination Chemistry and Organometallics
- Protease and Inhibitor Mechanisms
- Catalytic Cross-Coupling Reactions
- Asymmetric Synthesis and Catalysis
- Fibroblast Growth Factor Research
- Proteoglycans and glycosaminoglycans research
- Asymmetric Hydrogenation and Catalysis
- Oral microbiology and periodontitis research
- Catalytic C–H Functionalization Methods
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Cell Adhesion Molecules Research
- Synthesis of heterocyclic compounds
- Botanical Research and Chemistry
- Crystallography and molecular interactions
- Chemical synthesis and alkaloids
- Dermatologic Treatments and Research
- Peptidase Inhibition and Analysis
- Kruppel-like factors research
- Carbohydrate Chemistry and Synthesis
- RNA and protein synthesis mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Connective Tissue Growth Factor Research
University of York
2014-2024
Ecological Society of America
2023
Bionics Institute
2021
St Vincent's Hospital
2021
University of Leeds
2015-2016
University of British Columbia
2001-2013
Queen Mary University of London
2008
University of Edinburgh
2005-2006
Institute for Molecular Medicine Finland
2002
Helsinki University Hospital
2002
Abstract COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through combined mass spectrometry X-ray approach SARS-CoV-2 main protease, one two cysteine viral proteases essential replication. Our...
The regulation of cell shape, fibronectin mRNA level, secretion and assembly by substratum surface topography was investigated in early passage human gingival fibroblasts cultured on titanium-coated smooth or V-shaped grooved substrata produced micromachining. Cells surfaces were significantly elongated orientated along the grooves substratum, while height, measured using confocal scanning laser microscopy, approximately 1.5-fold greater than that cells surfaces. Northern hybridization...
The mechanism of tetracycline-induced inhibition matrix metalloproteinases (MMP) was studied by measuring the MMP secretion and MMP-2 mRNA levels in unkeratinizing periodontal ligament epithelial cells skin keratinocytes cultured presence doxycycline or chemically modified tetracyclines (CMT) lacking antimicrobial activity. Doxycycline, CMT-1, CMT-8 exerted a direct dose-dependent porcine cell medium activity as assayed gelatin enzymography. Both 92-kDa (MMP-9) 72-kDa (MMP-2) gelatinases...
A general and enantioselective synthesis of 2-substituted 2-phenylpyrrolidines -piperidines, an important class pharmaceutically relevant compounds that contain a quaternary stereocenter, has been developed. The approach involves lithiation-substitution enantioenriched N-Boc-2-phenylpyrrolidine or -piperidine (prepared by asymmetric Negishi arylation catalytic reduction, respectively). combined use synthetic experiments in situ IR spectroscopic monitoring allowed optimum lithiation...
. Established guidelines for safe levels of electrical stimulation neural prostheses are based on a limited range the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use these devices, highlighting need more carefully defined safety limits. We previously no adverse effects Pt corrosion products in cochleae guinea pigs following 4 weeks using charge densities far greater than published limits cochlear implants. The...
ABSTRACT Fusobacterium nucleatum is closely associated with human periodontal diseases and may also be a causative agent in other infections, such as pericarditis, septic arthritis, abscesses of tonsils liver. Initiation outcome infective depend critically on the host cell signaling system altered by microbe. Production proteinases infected cells an important factor pericellular tissue destruction migration. We studied binding F. to epithelial (HaCaT keratinocyte line) subsequent related...
A new method for the synthesis of enantiopure α-substituted piperazines via direct functionalization intact piperazine ring is described. The approach utilizes asymmetric lithiation-substitution an α-methylbenzyl-functionalized N-Boc using s-BuLi/(-)-sparteine or (+)-sparteine surrogate and provides access to a range (as single stereoisomers). Optimization methodology required detailed mechanistic study. Surprisingly, it was found that main culprits affecting yield enantioselectivity were...
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow design and synthesis of 56 3D disubstituted pyrrolidine piperidine fragments that occupy under-represented areas space (as demonstrated by principal moments inertia (PMI) analysis). A key, unique, underpinning feature this collection assessment shape...
Summary COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through combined mass spectrometry X-ray approach SARS-CoV-2 main protease, one two cysteine viral proteases essential replication. Our...
Understanding complex reaction systems is critical in chemistry. While synthetic methods for selective formation of products are sought after, oftentimes it the full signature, i.e., complete profile products/side-products, that informs mechanistic rationale and accelerates discovery Here, we report a methodology using high-throughput experimentation multivariate data analysis to examine signature one most complicated chemical reactions catalyzed by palladium known literature. A model...
The chemical and topographic effects of commercially pure titanium on cell morphology the regulation matrix metalloproteinase-2 (MMP-2) gene expression, synthesis, activity were investigated in early passage human gingival fibroblasts. Scanning electron microscopy showed that smooth (Ti), fibroblasts remained well spread randomly oriented throughout culture period. In contrast, cells V-shaped grooved (VTi) along grooves by 16 h proliferated this organization substratum surface chemistry...
OBJECTIVE: Bacterial pathogens involved in periodontal diseases exert a part of their destructive effect by triggering and inducing host cells to elevate secretion matrix metalloproteinases (MMPs). Pathogen‐secreted phospholipase (PLC) is one bacterial product that may trigger this response. The roles exogenous PLC leading the release, expression MMPs peripheral blood neutrophils (PMNs), cultured epithelial human gingiva porcine ligament were investigated. Also activities diseased healthy...
Structure-guided tethering of a fragment activator significantly increases enzyme activity.
[chemical reaction: see text]. 4-Hydroxypiperidin-2-ones may be prepared in highly diastereoselective fashion using a Cu(I)-catalyzed reductive aldol cyclization of alpha,beta-unsaturated amides with ketones. Used combination proline-catalyzed asymmetric Mannich reactions, this methodology enables the enantioselective synthesis more functionalized piperidin-2-ones and hydroxylated piperidines.
An 8-step, gram-scale synthesis of the (-)-sparteine surrogate (22 % yield, with just 3 chromatographic purifications) and a 10-step, (31 yield) are reported. Both syntheses proceed complete diastereocontrol allow access to either antipode. Since do not rely on natural product extraction, our work addresses long-term supply issues relating these widely used chiral ligands.
A synthetic approach to diverse natural product-like scaffolds was developed that broadly inspired by diterpene biosynthesis.
Keratinocyte growth factor (KGF) induction of keratinocyte attachment and migration on provisional basement membrane proteins was examined. KGF-treated keratinocytes showed increased to collagen types I IV fibronectin, but, not laminin-1, vitronectin, or tenascin. This increase time- dose-dependent. Increase in occurred with 2–10 μg/ml ECM proteins. KGF-stimulated cell β1 integrin-dependent but associated stimulation the surface expression nor affinity (activity) integrin receptor (α2β1)...
Abstract: The mechanism underlying a transition of the oral cavity mucosal epithelium towards susceptibility to opportunistic infections in HIV‐seropositive patients was investigated. Phenotypic markers CD1a, HLA‐DR, and CD86 Langerhans’ cells (LCs), p17 core protein human immunodeficiency virus (HIV), CD45RO memory T were labeled on hairy leukoplakia lesional biopsies clinically normal autologous tissue HIV‐infected patients. HIV detected association with LCs, mainly within epithelium....
Organolithiums have passed the test! Previously considered too reactive and unstable, organolithiums been tamed can now participate successfully in palladium-catalysed cross-coupling with aryl/vinyl bromides triflates.
Phospholipase C (PLC) is a putative virulence factor of several pathogenic bacteria. We studied if exogenous PLC would perturb epithelial behavior in infected tissues. Gelatin and casein zymography cell culture medium indicated that the broad-spectrum Bacillus cereus induced matrix metalloproteinase (MMP) production cells human skin (NHEK), gingiva (HGE), porcine periodontal ligament (PLE). In all three types, strongest increase (ninefold) at 0.1 U/ml was seen MMP-9 (92-kDa gelatinase)...
Lipopolysaccharide is a bacterial virulence factor implicated in chronic periodontitis, which may penetrate the junctional epithelial barrier and basement membrane to insult underlying stroma. We sought identify lipopolysaccharide-induced global gene expression changes responsible for signalling between stroma epithelium during disease onset.Using rat lipopolysaccharide periodontitis model, stromal tissue were separately collected from healthy diseased animals by laser-capture...