A5014265428- Synthesis and Catalytic Reactions
- Organic Chemistry Cycloaddition Reactions
- Chemical Reaction Mechanisms
- Fluorine in Organic Chemistry
- Cellular Mechanics and Interactions
- Chemical Synthesis and Reactions
- Crystallization and Solubility Studies
- Catalytic C–H Functionalization Methods
- X-ray Diffraction in Crystallography
- Viral Infections and Immunology Research
- Chemical Synthesis and Analysis
- Cell Image Analysis Techniques
- Cardiomyopathy and Myosin Studies
- Viral gastroenteritis research and epidemiology
- Cancer therapeutics and mechanisms
- Bioactive Compounds and Antitumor Agents
- Genetic Neurodegenerative Diseases
- SARS-CoV-2 and COVID-19 Research
- Cytokine Signaling Pathways and Interactions
- Carbohydrate Chemistry and Synthesis
- Asymmetric Hydrogenation and Catalysis
- Synthetic Organic Chemistry Methods
- Protein Tyrosine Phosphatases
- Advanced Fluorescence Microscopy Techniques
- PI3K/AKT/mTOR signaling in cancer
University of Pennsylvania
2021-2024
Penn Center for AIDS Research
2021
Translational Therapeutics (United States)
2021
Temple University
2018-2019
Charles River Laboratories (United Kingdom)
2019
Biocompatibles (United Kingdom)
2013
University of East Anglia
2007
Newcastle University
1974-2003
Philipps University of Marburg
1996
Marine Biological Association of the United Kingdom
1974
ABSTRACT Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2- ]pyrazin-3-yl)phenol. This exhibited broad spectrum activity, as it inhibited all tested species enteroviruses rhinoviruses, with 50% effective concentrations ranging between 4 71 nM. After...
Actin is one of the most abundant proteins in eukaryotic cells and a key component cytoskeleton. A range small molecules has emerged that interfere with actin dynamics by either binding to polymeric F-actin or monomeric G-actin stabilize destabilize filaments prevent their formation growth, respectively. Among these, latrunculins, which bind affect polymerization, are widely used as tools investigate actin-dependent cellular processes. Here, we report photoswitchable version latrunculin,...
Many eukaryotic genes play essential roles in multiple biological processes several different tissues. Conditional mutants are needed to analyze with such pleiotropic functions. In vertebrates, conditional gene inactivation has only been feasible the mouse, leaving other model systems rely on surrogate experimental approaches as overexpression of dominant negative proteins and antisense-based tools. Here, we have developed a simple straightforward method integrate loxP sequences at specific...
The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown pharmacological inhibition suppresses RAS/MAPK inhibit the proliferation RTK-driven cancer cell lines. Here, we describe first reported fragment-to-lead campaign against SHP2, where X-ray crystallography biophysical techniques were used to identify fragments binding multiple sites on SHP2....
Rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations asthma and chronic obstructive pulmonary disease. Other members genus can cause life-threatening acute neurological infections. There is currently no antiviral drug approved treatment such We have identified a series potent, broad-spectrum compounds that inhibit replication human rhinovirus, Coxsackie virus, poliovirus, enterovirus-71. The mechanism action has been established as inhibition lipid...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA New Approach to the Synthesis of .beta.-Hydroxy-.alpha.-amino Acids Using (Arylthio)nitrooxiranesRichard F. W. Jackson, Nicholas J. Palmer, Martin Wythes, William Clegg, and Mark R. ElsegoodCite this: Org. Chem. 1995, 60, 20, 6431–6440Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October...
Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and ERK1/2 kinases are positioned at a key node in this pathway, making them important targets for therapeutic intervention. Recently, number inhibitors have been advanced to investigational clinical trials patients with activating mutations B-Raf proto-oncogene or Ras. Here, we describe discovery candidate ASTX029 (15) through structure-guided optimization our previously published...
Visceral myopathy is a life-threatening disease characterized by muscle weakness in the bowel, bladder, and uterus. Mutations smooth γ-actin (ACTG2) are most common cause of disease, but mechanisms which mutations alter function unknown. Here, we examined four prevalent ACTG2 (R40C, R148C, R178C, R257C) that different severity spread throughout actin fold. R178C displayed premature degradation, R148C disrupted interactions with actin-binding proteins, R40C inhibited polymerization, R257C...
We report the first racemic and stereoselective synthesis of cis- trans-N-alkylaziridines viaN-chloroamines; using this methodology an N-3,4,5-trimethoxybenzylaziridine was synthesised efficiently cleaved, affording corresponding NH aziridine in high yield.
The scope and limitations of a method for the stereocontrolled synthesis range protected β-hydroxy-α-amino acids have been established. comprises condensation chiral, enantiomerically pure aldehyde 6 with (4-methylphenylthio)nitromethane 7 to form 1-arylthio-1-nitroalkene 8; stereoselective epoxidation this alkene metal alkyl peroxide; stereospecific reaction arylthionitrooxirane nitrogen nucleophile give an α-amino thioester. This has employed in derivatives both diastereoisomers threonine...
Epoxidation of the 1-nitro-1-(p-tolylthio)alkene 1 derived from D-isopropylideneglyceraldehyde with lithium tert-butyl peroxide affords syn epoxide 2 moderate selectivity, whereas epoxidation potassium anti diastereoisomer 3 preferentially; treatment each epoxides and amines, including ammonia, gives diastereoisomerically pure α-amino thioesters no trace stereoisomeric contamination.
A series of pyrrolidine amino nitrile DPP1 inhibitors have been developed and characterized. The S2 pocket structure-activity relationship for these compounds shows significant gains in potency from interacting further with target residues a network water molecules the binding pocket. Herein we describe X-ray crystal structures several alongside an analysis factors influencing inhibitory toward which stabilization network, demonstrated using Grand Canonical Monte Carlo simulations free...
Polyoxamic acid 4a is prepared by a short and efficient process in which the key steps are highly diastereoselective nucleophilic epoxidation of D-threitol-derived alkene 6 using potassium tert-butylperoxide, followed reaction oxirane 7a with ammonia.