PhD in Chemical Biology – Synthesis of macrocyclic peptidomimetics: Next Generation Tools for Modulating High Value Drug Targets

Start Date: 01 October 2025

Macrocyclic peptidomimetics represent a transformative approach in drug discovery, bridging the gap between small molecules and biologics. These advanced, conformationally constrained molecules mimic the structural and functional characteristics of natural peptides while overcoming their limitations, such as poor stability, low bioavailability, and susceptibility to proteolysis. This project focuses on the computational design, chemical synthesis, and evaluation of macrocyclic peptidomimetics as precision tools to target high-value drug targets.  

Using innovative cyclisation strategies, including diyne-girder stapling (RSC Chem. Bio., 2025 (doi: 10.1039/D4CB00288A) & Chem. Eur. J., 2023, 29, e202300855) and triazole based disulfide bridge surrogates (Chem. Sci., 2019, 10, 1671), this research will generate stable, cell-permeable macrocycles with enhanced binding affinity and specificity. Computational modeling and Virtual Reality visualisation will guide the design of these molecules, while advanced robotic solid-phase synthesis equipment will be used to produce the peptidomimetics. Structural characterisation is achieved using NMR, circular dichroism and mass spectrometry, and functional properties elucidated using fluorescence polarisation, SPR and physiologically relevant cell-based assays, focusing on restoring dysregulated pathways and disrupting pathological protein-protein interactions. 

Innovation and entrepreneurship will be key aspects of this project, making it an ideal fit for students seeking an applied synthetic organic chemistry project with a strong focus on drug discovery. The project will be conducted within the Jamieson group, which is based in the state-of-the-art Advanced Research Centre (ARC), providing access to cutting-edge facilities and a dynamic interdisciplinary research environment. 

 How to Apply:  Please refer to the following website for details on how to apply: 

https://www.gla.ac.uk/postgraduate/research/chemistry/