A5063722947- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Genetic Neurodegenerative Diseases
- Signaling Pathways in Disease
- Blood properties and coagulation
- Monoclonal and Polyclonal Antibodies Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Enzyme Structure and Function
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
Newcastle University
2022-2024
Cancer Research UK
2022
Cardiff University
2017
Spinocerebellar ataxia type 35 (SCA35) is a rare autosomal-dominant neurodegenerative disease caused by mutations in the TGM6 gene, which codes for transglutaminase 6 (TG6). Mutations TG6 induce cerebellar degeneration an unknown mechanism. We identified seven patients bearing new TGM6. To gain insights into molecular basis of mutant TG6-induced neurotoxicity, we analyzed all mutants and five previously linked to SCA35. found that wild-type (TG6-WT) protein mainly localized nucleus...
Optimisation of the affinity lead compounds is a critical challenge in identification drug candidates and chemical probes process that takes many years. Fragment-based discovery has become established as one methods choice for starting with small, low compounds. Due to their affinity, evolution fragments desirable levels often key challenge. The accepted best method increasing potency by iterative fragment growing, which can be very time consuming complex. Here, we introduce paradigm hit...
The development of ligands for biological targets is critically dependent on the identification sites proteins that bind molecules with high affinity. A set compounds, called FragLites, can identify such sites, along interactions required to gain affinity, by X-ray crystallography. We demonstrate utility FragLites in mapping binding bromodomain BRD4 and ATAD2 FragLite comparable a full fragment screen identifying ligand key interactions. extend analogous compounds derived from amino acids...
High-throughput screening provides one of the most common ways finding hit compounds. Lead-like libraries, in particular, provide hits with compatible functional groups and vectors for structural elaboration physical properties suitable optimization. Library synthesis approaches can lead to a lack chemical diversity because they employ parallel derivatization building blocks using single reaction types. We address this problem through "build-couple-transform" paradigm generation lead-like...
Abstract Optimisation of the affinity lead compounds is a critical challenge in identification drug candidates and chemical probes. Fragment-based discovery has become established as one methods choice for starting with small, low compounds. Due to their affinity, evolution fragments desirable levels often key challenge. The accepted best method increasing potency by iterative fragment growing, which can be very time consuming. Here, we introduce paradigm optimisation using poised...