Chemical Biology
Our pioneering protecting-group chemistry that enabled the solid-phase synthesis of chimeric and cyclic peptides has contributed to interactions with Isabel Haro (CSIC, Barcelona) over the past 6 years in establishing peptoid-based immunodiagnostic agents for hepatitis A and G viruses.
This successful collaboration recently resulted in the award of a grant to design and synthesise new peptoids for use not only in the diagnosis of HGV infection, but also to determine the mechanism of HGV-mediated delayed development of AIDS in HIV infected patients.
A noteworthy collaborative project was recently established with John Mayer (University of Nottingham), in the chemical biology and molecular diagnostics for neurodegenerative diseases.
In a recently funded CRUK project with Jonas Emsley and Peter Fischer, novel 'chemically' stable heterotrimeric collagen peptides will be chemically constructed to determine the mechanism of molecular recognition by specific integrin 1 receptors.
Fluorescent Ligands for Single Cell Pharmacological Measurements
A hugely successful collaborative project between the Institute of Cell Signalling (Prof Steve Hill) and the Division of Medicinal Chemistry and Structural Biology, (Dr B Kellam), funded by the Wellcome Trust, the BBSRC and the University of Nottingham, has generated exciting insight into the visualisation and molecular pharmacology of G-Protein coupled receptors (GPCRs) in their natural habitat, i.e. the lipid membrane of intact living cells.
By designing, synthesising and validating pharmacologically active fluorescently tagged derivatives of both neurotransmitters and drug molecules, we have been able to successfully employ these to visualise the location of their receptor target within cell surface microdomains at the single cell level. Furthermore, since their binding to the receptor is reversible we have been able to obtain detailed pharmacological information such as affinity using single-molecule detection techniques such as Fluorescence Correlation Spectroscopy (FCS).
When coupled to the growing exploitation of fluorescence-based readouts in high throughput and high content screening, it is clear that fluorescent molecules offer a safer, more powerful and more versatile alternative to radioligands in molecular pharmacology and drug discovery. To this end we have established robust intellectual property surrounding both our newly developed fluorescent ligands and their exploitation in various homogeneous high content screening assays, and this rich IP platform has facilitated the recent successful establishment of the spin-out company CellAura Technologies Ltd.