A5074639728- NMR spectroscopy and applications
- Ubiquitin and proteasome pathways
- Advanced NMR Techniques and Applications
- Cellular Mechanics and Interactions
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Advanced MRI Techniques and Applications
- Cellular transport and secretion
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Protein purification and stability
- Toxin Mechanisms and Immunotoxins
- Protein Degradation and Inhibitors
- Molecular spectroscopy and chirality
- Tuberculosis Research and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Synthesis of Tetrazole Derivatives
- Drug Transport and Resistance Mechanisms
- Electrostatics and Colloid Interactions
- Proteoglycans and glycosaminoglycans research
- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
University of East Anglia
2017-2024
Norwich Research Park
2018-2024
Cancer Research UK Scotland Institute
2022-2024
Horizons Clinical Research Center
2024
Edinburgh Cancer Research
2024
University of Rome Tor Vergata
2011-2023
The University of Texas Medical Branch at Galveston
2019-2020
Catholic University Our Lady of Good Counsel
2016
Chiesi (France)
2014
In-Q-Tel
2012
Increased glycolytic flux is a common feature of many cancer cells, which have adapted their metabolism to maximize glucose incorporation and catabolism generate ATP substrates for biosynthetic reactions. Indeed, glycolysis allows rapid production provides metabolic intermediates required cells growth. Moreover, it makes less sensitive fluctuations oxygen tension, condition usually occurring in newly established tumor environment. Here, we provide evidence dual role MAPK14 driving...
STD NMR spectroscopy is a powerful ligand-observed tool for screening and characterizing the interactions of small molecules low molecular weight fragments with given macromolecule, identifying main intermolecular contacts in bound state. It also analytical technique accurate determination protein–ligand dissociation constants (KD) medium-to-weak affinity, interest pharmaceutical industry. However, KD epitope mapping requires long series experiments at increasing saturation times to carry...
All mRNAs require eukaryotic translation initiation factor (eIF) 4A1 for through its different functions: loading of the pre-initiation complex onto and unwinding RNA structure. eIF4A1 is catalytic subunit cap binding eIF4F presumed to select these activities, instructed by signalling pathways driving cell fate. The mechanisms underlying activation distinct functions establish translational selectivity are unknown. Here, we have unravelled complexity mRNA selection eIF4A1. We mechanistically...
Activating mutations of Ras are one the most prevalent drivers cancer and often associated with poor clinical outcomes. Despite FDA approval for two irreversible inhibitors that target inactive state KRasG12C, significant unmet need still exists, susceptibility non-G12C mutants to inactive-state inhibition remains unclear. Here we report discovery a novel series reversible bind in an enlarged version switch I-II pocket nanomolar affinities. Dependent on chemotype these can either...
Natural allyl sulfur compounds show antiproliferative effects on tumor cells, but the biochemical mechanisms underlying antitumorigenic properties of organ are not yet fully understood. Sodium 2-propenyl-thiosulfate is a garlic water-soluble organo-sulfane compound able to promote apoptosis in cancer affecting 'managing' redox state cell. Our studies that sodium reacts spontaneously with reduced glutathione at physiological pH, leading formation S-allyl-mercapto-glutathione, radicals and...
Low-affinity protein-ligand interactions are important for many biological processes, including cell communication, signal transduction, and immune responses. Structural characterization of these complexes is also critical the development new drugs through fragment-based drug discovery (FBDD), but it challenging due to low affinity fragments binding site. Saturation transfer difference (STD) NMR spectroscopy has revolutionized study low-affinity receptor-ligand enabling detection structural...
RTN1-C protein is a membrane localized in the ER and expressed nervous system. Its biological role still unclear, although interactions of N-terminal region with proteins involved vesicle trafficking have been observed, but C-terminal this family remains to be investigated. By homology analysis amino acid sequence, we identified unique consensus sequence characteristic H4 histone protein. Thus, 23-mer peptide (RTN1-CCT) corresponding residues 186−208 was synthesized, its conformation...
Thymosin α1 is a peptidic hormone with pleiotropic activity and used in the therapy of several diseases. It unstructured water solution interacts negative regions vesicles by assuming two tracts helical conformation structural break between them. This study reports on α1's interaction mixed phospholipids phosphatidylcholine phosphatidylserine, component membranes, ¹H natural abundance ¹⁵N nuclear magnetic resonance (NMR). The results indicate that occurs when membrane negatively charged...
Lactobacillus reuteri is a gut symbiont inhabiting the gastrointestinal tract of numerous vertebrates. The surface-exposed serine-rich repeat protein (SRRP) major adhesin in Gram-positive bacteria. Using lectin and sugar nucleotide profiling wild-type or L. isogenic mutants, MALDI-ToF-MS, LC-MS GC-MS analyses SRRPs, we showed that strains 100-23C (from rodent) ATCC 53608 pig) can perform O-glycosylation modify SRRP100-23 SRRP53608 with Hex-Glc-GlcNAc di-GlcNAc moieties, respectively....
Due to a high density of negative charges on its surface, DNA condenses cations as counterions, forming the so-called "ion atmosphere". Although release counterions upon DNA-protein association has been postulated have major contribution binding thermodynamics, this remains be confirmed through direct observation ions. Herein, we report characterization ion atmosphere around using NMR spectroscopy and directly detect association. NMR-based diffusion data reveal highly dynamic nature within...
Thymosin α1 (Tα1) is a peptide hormone whose therapeutic application has been approved in several diseases, but the description of precise receptor for its action still remains elusive and some knowledge mechanism interaction with cell membrane needs to be clarified. This work aimed at studying folding Tα1, which completely unstructured water solution, model membranes.The Tα1 sodium dodecyl sulfate micelles was monitored by NMR CD spectroscopy techniques.Tα1 assumes helical conformation...
Inclusion of drugs in cyclodextrins (CDs) is a recognized tool for modifying several properties such as solubility, stability, bioavailability, and so on. The photoreactive behavior the β-CD/ketoprofen (KP) complex upon UV exposure showed significant increase photodecarboxylation, whereas secondary degradation products by hydroxylation benzophenone moiety were inhibited. results may account an improvement KP photophysical inclusion, thus better fostering its topical use. To correlate...
Ubiquitin binding domains (UBDs) are modular elements that bind non-covalently to ubiquitin and act as downstream effectors amplifiers of the ubiquitination signal. With few exceptions, UBDs recognize hydrophobic path centered on Ile44, including residues Leu8, His68, Val70. A variety different orientations, which can be attributed specific contacts between each UBD surface surrounding patch, specify how class specifically ubiquitin. Here, we describe structural model a novel...
Humic substances (HS) are the largest constituent of soil organic matter and considered as a key component terrestrial ecosystem. HS may facilitate transport inorganic molecules, well sorption interactions with environmentally relevant proteins such prions. Prions enter environment through shedding from live hosts, facilitating sustained incidence animal prion diseases Chronic Wasting Disease scrapie in cervid ovine populations, respectively. Changes structure upon environmental exposure be...
RTN1-C protein is a membrane localized in the ER and expressed nervous system, its biological role not completely clarified. Our previous studies have shown that C-terminal region of RTN1-C, corresponding to fragment from residues 186 208, was able bind nucleic acids interact with histone deacetylase (HDAC) enzymes. In present work properties synthetic RTN1-C(CT) peptide this were studied relation ability metal ions N-terminal region. characterized by presence high-affinity copper nickel ion...
Abstract Differential epitope mapping saturation transfer difference (DEEP‐STD) NMR spectroscopy is a recently developed powerful approach for elucidating the structure and pharmacophore of weak protein–ligand interactions, as it reports key information on orientation ligand architecture binding pocket. The method relies selective protein residues in site generation differential map by observing ligand, which depicts nature making contact with bound state. Selective requires knowledge...
Fluid biphasic systems are one of the most interesting dynamic in chemistry and biochemistry. In nuclear magnetic resonance (NMR) spectroscopy, study solute dynamics across fluid requires introduction dedicated NMR methods, due to their intrinsic heterogeneity. Diffusion spatially resolved techniques represent a useful approach for dealing with solutes have been applied lately success. Nevertheless, other potential applications spectroscopy remain be explored. this proof-of-concept...
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