Our main research achievements were in the areas of medicinal chemistry of sulphur containing compounds (Hamilton), macrocycles (Matthews) and natural product compounds (Gibbons).
In chemical biology, our current research strengths lie in understanding of assembly of DNA and its alternative motives (Waller), protein-protein interactions (Searcey, Beekman) and epigenetics (Ganesan).
These lines of research are supported by UKRI (EPSRC (Searcey); BBSRC (Searcey, Ganesan), industrial funding (Hamilton, Ganesan), Big C (Searcey), Royal Society and British Council (Matthews, Ganesan). Ganesan was the lead of EU funded COST action Epigenetic Chemical Biology (EPICHEM).
- By using an in vivo mouse model of lung infection we demonstrated that our novel Calixarene-based glycoclusters functionalized with galactosides or fucosides provided an almost complete protection against Pseudomonas aeruginosa (Matthews).
- As part of interdisciplinary team (UCL, Southampton, Hong-Kong, UEA), Ganesan showed that NAADP signalling plays a major role in reperfusion-induced cell death and represents a potent pathway for protection against reperfusion injury.
- Searcey and Beekman discovered a highly efficient approach to the development of inhibitors of the p53/hDMX or hDM2 interaction that involves the design of small molecules in silico based upon a peptide/protein structure.
- Hamilton made significant advances in understanding the role of bacillithiol, the main thiol metabolite in many Gram-positive bacteria, including identification of its derivatives, studying mechanisms of their synthesis and analysis of genome data.
- Considerable breakthroughs were achieved in understanding structure-activity relationship of Diphyllin and its derivatives (cytotoxic natural products structurally related to the anti-cancer drug podophyllotoxin) upon human melanoma cells (Gibbons).
This research cluster is led by Professor Ganesan.
Dr Andrew BeekmanDr Beekman’s expertise lies in the development of new methods and discovering new pharmaceutical leads to target protein-protein interactions. Dr Beekman's research also includes designing new molecular recognition structures for delivery of cytotoxic warheads.
Prof GanesanProf Ganesan’s research area is in the organic synthesis of biologically active natural products. Prof Ganesan also has interests in the synthesis of epigenetic enzyme inhibitors for cancer and infectious diseases, and the synthesis of therapeutically relevant protease inhibitors, calcium signalling probes and antibiotics.
Prof Simon GibbonsProf Gibbons Medicinal research investigates natural products, phytochemistry and antimicrobial natural products from plants and microbes. In addition to studying compounds that modify bacterial resistance such as plasmid transfer inhibitors or efflux inhibitors Prof Gibbon’s lab have expertise in the isolation and structure elucidation of natural products that are active against drug-resistant bacteria, and the characterisation of natural and synthetic new psychoactive substances from crude plant or fungal materials or single natural or synthetic chemical entities.
Dr Chris HamiltonDr Hamilton’s research encompasses the study of chemical and biochemical functions of low molecular weight thiols in Gram positive bacteria, redox mechanisms of bioactive organosulfur metabolites from garlic and mechanistic enzymology.
Dr Susan MatthewsDr Matthews’ research includes the investigation of small molecule antibiotics and antioxidants, anti-adhesive antibiotics based on macrocyclic platforms, multicalixarene gene delivery vectors, fluorescent probes for understanding cellular uptake and stimuli responsive materials for drug delivery.
Dr Paul McDermottThe synthesis of Symplostatin 4 analogues for QSAR studies and the synthesis of Simocyclinone D8 analogues as potential antibiotics are the research interests of Dr McDermott.
Prof Mark SearceyProf Searcey’s research group studies the targeting of DNA as a potential route to therapeutically useful molecules as anti-cancer agents, the synthesis of new molecules for medicinal chemistry and new approaches to targeting PPIs. Prof Searcey is also developing nanotechnology approaches to targeting via peptides and antibodies.