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Protein–protein interactions play central roles in cancer initiation, progression, and therapeutic resistance, yet they remain among the most challeng... Role: Postdoctoral Research Associate (SS13437), Category: Scientific
Postdoctoral Research Associate (SS13437): (Company Name - Subscribers only)
Protein–protein interactions play central roles in cancer initiation, progression, and therapeutic resistance, yet they remain among the most challenging targets in drug discovery. Many oncogenic PPIs involve large, flat, and dynamic interfaces that are poorly addressed by conventional small molecules. Beyond Rule of 5 (bRo5) macrocyclic compounds, particularly highly constrained peptides, offer a powerful strategy to engage these challenging targets by combining the binding surface area of biologics with the tunability and cell permeability of small molecules.
Working with members of the Lovell lab, the successful candidate will contribute to the development of next-generation macrocyclic inhibitors designed to disrupt cancer-relevant protein–protein interactions. The project will focus on the design, synthesis, and biological evaluation of structurally constrained peptide macrocycles that access bRo5 chemical space while maintaining favourable pharmacological properties.
A key feature of this project is the use of continuous-flow chemistry to enable the efficient, reproducible, and scalable synthesis of complex macrocyclic peptides. Flow-based approaches will be employed to control reaction kinetics, improve cyclisation efficiency, and accelerate structure–activity relationship (SAR) exploration. These compounds will be integrated into direct-to-biology workflows for rapid functional screening against cancer targets.
The project will involve a multidisciplinary toolkit, including:
- Continuous-flow synthesis of highly constrained macrocyclic peptides
- Advanced peptide cyclisation and stapling strategies
- Direct-to-biology screening approaches for PPI inhibition
- Biophysical and biochemical assays to validate target engagement
- Close collaboration with chemical biology and cancer biology researchers
This work aims to expand the druggable landscape of cancer by delivering innovative bRo5 macrocyclic modalities capable of modulating previously intractable protein–protein interactions.
As a member of Research Staff at the (Company Name - Subscribers only), you will be encouraged to take up a minimum of 10 days professional development pro rata per year