The Vendrell lab has developed a new method that allows for fluorescent probes to light up when bound to targets of interest on the cell surface. Using their method, they identified a lead peptide that could bind to an immune cell target and found the drug avasimibe affects immune cell behaviour important in cancer, multiple sclerosis and rheumatoid arthritis. Their method has huge potential to speed up and improve drug discovery. We can study where specific molecules are located in our body’s cells, and how they behave over time. By designing a fluorescent probe that can recognise and bind to specific targets of interest within and around cells, we can watch the fluorescence down a microscope. These probes can by designed by attaching a ready-made fluorescent dye to a small molecule called a peptide. However, this approach needs long incubation times to ensure sufficient binding, and requires washing steps to remove unbound dye, otherwise you will see fluorescence all the time, regardless of whether the probe has bound to the target. Another option is for the peptide building blocks called amino acids to contain weakly fluorescent groups that increase fluorescence when the peptide binds to its target. These are called fluorogenic amino acids, and their “turn-on” behaviour makes it possible to image cells without washing away excess probe. However, currently their fluorescence is not very bright and there are no ways to generate multicolour fluorescent building blocks compatible with wash-free experiments. Monitoring specific biological activity with new method In this study, IRR Group Leader Marc Vendrell and colleagues developed a strategy to engineer a large collection of multicolour fluorogenic amino acids using chemistry techniques. The team, a collaboration of IRR scientists with Singapore University of Technology and Design, Osaka University, Nanyang Technological University, and industry partner Concept Life Sciences Ltd, engineered these probes to target a cell-surface receptor called PD-1 found on immune cells called T cells. The behaviour of T cells is modulated by PD-1, and abnormal PD-1 signalling is associated with diseases including cancer and autoimmune disorders. They found that with their method, one particular lead peptide bound to PD-1, and acted as a turn-on switch to give excellent brightness. They could then visualise levels of PD-1 receptors on T cells by its fluorescence. Identifying a drug that modulates immune cell activity The team then used the turn-on properties of their lead peptide to develop a general method that monitors PD-1 levels in human T cells after treatment with multiple immune-modulating drugs. Using their method, they identified the previously unreported role of avasimibe as a drug that reduces PD-1 levels in T cells and affects their behaviour. This shows the method can enable T cell targeted drug screening. Our fluorogenic amino acids could accelerate the discovery of pharmacological structures targeting the PD-1 pathway, a pathway involved in cancer, rheumatoid arthritis and multiple sclerosis. Prof Marc Vendrell IRR Group lead and the paper’s corresponding author Microscopy images showing lead fluorogenic peptide (red) binds to PD-1 cell-surface receptor on T-cells when activated (right), but not when T cells are inactive (left). This work establishes a versatile and scalable approach for designing multicolour fluorogenic peptides, that can label a wide range of biological targets. This paves the way for advanced imaging tools, large-scale screening and immunotherapy drug discovery. This work was funded by Medical Research Scotland, the Ministry of Education, Singapore and the European Research Council. Related links Read the full article in Nature ChemistryVendrell research group Dynafluors website Tags CIR This article was published on Thursday 20 August 2026
