A5081543239- Trypanosoma species research and implications
- Calcium signaling and nucleotide metabolism
- Malaria Research and Control
- Venomous Animal Envenomation and Studies
- Rabies epidemiology and control
- Ion channel regulation and function
- Computational Drug Discovery Methods
- Cancer therapeutics and mechanisms
- Bioactive Natural Diterpenoids Research
- Toxin Mechanisms and Immunotoxins
- Pharmacogenetics and Drug Metabolism
- Biochemical and Molecular Research
- Ion Transport and Channel Regulation
- Chronic Lymphocytic Leukemia Research
- Synthesis and Catalytic Reactions
- Nicotinic Acetylcholine Receptors Study
- Mosquito-borne diseases and control
- Polydiacetylene-based materials and applications
- Bone and Dental Protein Studies
- Supramolecular Self-Assembly in Materials
University of Liverpool
2020-2025
Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left life-long sequelae. Current antivenom therapies have several limitations including high cost, variable cross-snake species efficacy and a requirement for intravenous administration clinical setting. Next-generation snakebite are being widely investigated the aim improve efficacy, safety. In recent years small molecule drugs shown considerable promise indication, oral bioavailability...
Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. demonstrate TbAQP2’s unique architecture permits permeation through its central how specific mutations highly conserved motifs affect drug permeation. Introduction of key amino acids into renders latter permeable pentamidine. Molecular dynamics demonstrates by...
Snakebite envenoming is a neglected tropical disease that causes as many 1.8 million envenomings and 140,000 deaths annually. To address treatment limitations exist with current antivenoms, the search for small molecule drug-based inhibitors can be administered early interventions has recently gained traction. Snake venoms are complex mixtures of proteins, peptides molecules their composition varies substantially between within snake species. The phospholipases A2 (PLA 2 ) one main...
Abstract The prediction of gelation is an important target, yet current models do not predict any post‐gel properties. Gels can be formed through the self‐assembly many molecules, but close analogs often form gels. There has been success using a number computational approaches to understand and from molecular structures. However, these focus on whether or gel will form, properties resulting Critically, it gels that are for specific application, simply formed. Supramolecular kinetically...
Snakebite envenoming is a neglected tropical disease that causes high mortality and morbidity. The current treatment, intravenous antivenom, comes with numerous disadvantages making new therapeutics important. Optimised small molecules offer the possibility for oral use at onset of envenoming, highly pathogenic, zinc-dependent, snake venom metalloproteinase toxin family represents an attractive target drug discovery. Through systematic chemical modification guided by molecular modelling, we...
We report the synthesis and biological profiling of photoreactive chemical probes based on an established plasmepsin X inhibitor scaffold. Maintained antimalarial recombinant enzyme activity support their use in future proteomic studies.
Synthetic endoperoxide antimalarials, such as 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes, are promising successors for current front-line semisynthetic artemisinin derivatives. However, limited solubility of second-generation analogues in biological-relevant media represents a barrier clinical development. We present methodology the synthesis nonlinear tetraoxane antimalarials E209 N205 to investigate reduced molecular symmetry on vitro antimalarial activity physicochemical properties. While...
Abstract Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. demonstrate TbAQP2’s unique architecture permits permeation through its central how specific mutations highly conserved motifs affect drug permeation. Introduction of key amino acids into renders latter permeable pentamidine. Molecular dynamics...