A5016086535- Synthetic Organic Chemistry Methods
- Marine Sponges and Natural Products
- X-ray Diffraction in Crystallography
- Chemical synthesis and alkaloids
- Crystallization and Solubility Studies
- Synthesis of Organic Compounds
- Asymmetric Synthesis and Catalysis
- Organic Chemistry Cycloaddition Reactions
- Carbohydrate Chemistry and Synthesis
- Advanced Synthetic Organic Chemistry
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- Fluorine in Organic Chemistry
- Bioactive Compounds and Antitumor Agents
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Breastfeeding Practices and Influences
- Genomics, phytochemicals, and oxidative stress
- Child Nutrition and Water Access
- Sulfur-Based Synthesis Techniques
- Synthesis and Catalytic Reactions
- Synthesis and biological activity
- Synthesis of heterocyclic compounds
- Synthesis and Biological Evaluation
- Catalytic C–H Functionalization Methods
- Synthesis and Biological Activity
University of Manchester
2014-2024
Institute of Organic Chemistry
2017
Cancer Research UK Manchester Centre
2011
Respiratory Clinical Trials
2010
University of Cambridge
2007
University of Reading
1997-2000
University of Oxford
1964-1999
Dyson (United Kingdom)
1992-1998
MRC Human Nutrition Research
1997
University of Colorado Denver
1997
Production and trafficking of proteins entering the secretory pathway eukaryotic cells is coordinated at endoplasmic reticulum (ER) in a process that begins with protein translocation via membrane-embedded ER translocon. The same complex also responsible for co-translational integration membrane orchestrates polypeptide modifications are often essential function. We now show previously identified inhibitor ER-associated degradation (ERAD) eeyarestatin 1 (ESI) potent translocation. have...
The synthesis is reported here of two novel series inhibitors human NAD(P)H quinone oxidoreductase-1 (NQO1), an enzyme overexpressed in several types tumor cell. first comprises substituted symmetric dicoumarol analogues; the second contains hybrid compounds where one 4-hydroxycoumarin system replaced by a different aromatic moiety. Several show equivalent or improved NQO1 inhibition over dicoumarol, both presence and absence added protein. Further, correlation demonstrated between ability...
The development of efficient and sustainable methods for the synthesis nitrogen heterocycles is an important goal chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds precursors. A potential biocatalytic approach this privileged scaffold would be asymmetric dearomatization readily assembled activated pyridines. However, nature yet yield a suitable biocatalyst specifically reaction. Here, by combining...
Abstract Normal subjects showed a right hemisphere processing superiority in reaction times to visual stimuli under conditions of sustained attention. This asymmetry was predicted based on findings studies blood flow, clinical populations, and physiology lateralization the noradrenergic system. The eliminated when an auditory event delivered simultaneously with target suggesting common pathway between voluntary alerting more automatic effects external stimuli. act sustaining alertness also...
An exciting new family of hydrophilic ligands for the selective extraction Am(<sc>iii</sc>) from spent nuclear fuel are reported herein.
The first examples of 4,7-disubstituted 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzo-triazin-3-yl)-1,10-phenanthroline (CyMe4-BTPhen) ligands are reported herein. Evaluating the kinetics, selectivity and stoichiometry actinide(iii) lanthanide(iii) radiotracer extractions has provided a mechanistic insight into extraction process. For time, it been demonstrated that metal ion kinetics can be modulated by backbone functionalisation promising new CHON compliant candidate ligand...
Highlights•ES1, ES2, and ES24 deplete Ca2+ in ER•ESR35 ES47 do not affect cellular homeostasis•The most potent eeyarestatin, ES24, comprises only the 5-nitrofuran domain•ES1 target Sec61 complexes ERSummaryEeyarestatin 1 (ES1) inhibits p97-dependent protein degradation, Sec61-dependent translocation into endoplasmic reticulum (ER), vesicular transport within endomembrane system. Here, we show that ES1 impairs homeostasis by enhancing leakage from mammalian ER. A comparison of various analogs...
The biomimetic synthesis of a pentacyclic alkaloid (keramaphidin B, 1), an intermediate in the biogenetic pathway to manzamine alkaloids, has been achieved. Compound 1 was formed by intramolecular Diels-Alder reaction macrocycle 2 buffer followed reduction with NaBH4 . This provides first direct expeimental evidence for authors' biosynthetic hypothesis.
Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator ER (endoplasmic reticulum) function. In present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), causes production mislocalized polypeptides are ubiquitinated and degraded. Unexpectedly, our results suggest these non-translocated promote activation UPR (unfolded protein response), indeed can...
Background The small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin Shiga/Shiga-like toxins (SLTx) are endocytosed trafficked to ER. Their catalytic subunits thought utilise ERAD-like mechanisms dislocate from ER into cytosol, where a proportion uncouples process, recovers conformation destroys their cellular targets. We therefore investigated ESI...
A broad range of 1,10-phenanthroline substrates was efficiently C-H functionalised, providing rapid, gram-scale access to substituted heteroaromatic cores utility. Furthermore, this functionalisation pathway extended the synthesis previously inaccessible, ultra-soluble, 2,9-bis-triazinyl-1,10-phenanthroline (BTPhen) ligands for advanced nuclear fuel cycles.
Eeyarestatin 24 (ES24) is a promising new antibiotic with broad-spectrum activity. It shares structural similarity nitrofurantoin (NFT), yet appears to have distinct and novel mechanism: ES24 was found inhibit SecYEG-mediated protein transport membrane insertion in Gram-negative bacteria. However, possible additional targets not been explored. Moreover, its activity notably better against Gram-positive bacteria, for which mechanism of action had investigated. We used transcriptomic stress...
NAD(P)H quinone oxidoreductase-1 (NQO1) is a homodimeric protein that acts as detoxifying enzyme or chaperone protein. Dicourmarol interacts with NQO1 at the binding site and can both inhibit activity modulate interaction of other proteins. We show dicoumarol related compounds to generates negative cooperativity between monomers. This does not occur in presence reducing cofactor, NAD(P)H, alone. Alteration Gly150 (but Gly149 Gly174) abolished dicoumarol-induced cooperativity. Analysis...