The Department of Biochemistry’s seminar series will continue Tuesday 3rd December at 12:00pm in the Jean Thomas Lecture Theatre:
Our next talk is by Gustavo Bezerra (BicycleTx Ltd ), who will give a seminar entitled “Revitalising antiviral strategies: Bicycle molecules as a new therapeutic modality”.
Gustavo is hosted by Dima Chirgadze (dyc21@cam.ac.uk) who can be contacted for one-to-one meetings.
Abstract: COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles’ inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization.
Hector Newman (BicycleTx Ltd ), will also give a seminar entitled “Development of novel non-covalent inhibitors of PBP3 (Bicycle® molecules) as antimicrobials against clinically-relevant Enterobacterales”.
Hector is also hosted by Dima Chirgadze (dyc21@cam.ac.uk) who can be contacted for one-to-one meetings.
Abstract: Penicillin binding proteins (PBP) remain an attractive antimicrobial target, but the prevalence of beta lactamase driven resistance and, more rarely, target-based mutations, necessitates new classes of PBP-targeting drugs. BicycleTx have identified high affinity, non covalent inhibitors of E. coli PBP3 using their proprietary phage-screening platform (Bicycles®).
EcPBP3 was highly tractable to the Bicycle platform, and peptides of interest from selections against Escherichia coli PBP3 were chemically synthesised and characterised using fluorescence polarisation, SPR, MIC and cytotoxicity assays. We describe a Bicycle peptide with high-affinity binding of E. coli PBP3 and a viable spectrum of killing activity against clinically relevant Enterobacteriales species. Insights from crystallography were using to optimise the target binding and DMPK properties of peptide derivatives of the hit from phage screening. We present updates on the further development of the compound series. Our Bicycle peptide represents a novel non-covalent inhibitor of E. coli PBP3
We encourage all Departmental scientists, students, and anyone interested to attend the Tea Club seminars.
Please note that this seminar series takes place in person only.