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Lecture

CBI Lecture: Chemical Probes for Precision Medicine

Date
Friday 21 February 2025
Time
Location
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden
Room
CM.3.23

It is our great pleasure to invite you to the lecture of Prof. Dr. Marc Vendrell of the University of Edinburgh. For a long time, Prof. Vendrell has been a key innovator in the field of fluorophore development for biological application. In close conjunction with the clinical departments at the university hospital where he resides, he been developing, and synthesizing, new molecules for detecting specific biological events, such as the infection with pathogens, the induction of cell death by T-cells, and the activation of cells by cytokines. His combination of boundary-pushing chemistry and imaging, and their application to close-to-clinical biological problems, make us delighted to have him as a CBI speaker.

Abstract

Fluorescent activatable probes are valuable tools for live-cell imaging because of their tunability and target specificity.1 Our group has designed a collection of fluorogenic amino acids and peptides for high-resolution biological imaging and translational medicine, which was recognized with the RSC Bader Prize 2023. Our team have demonstrated that this approach can be used to generate probes to visualize infectious pathogens (e.g., fungal pathogens in ex vivo human lung tissue2) and subsets of immune cells in live cells and in vivo3 and in ex vivo human biopsies.4

We have designed our fluorescent amino acids to: 1) be compatible with conventional solid-phase peptide synthesis, 2) maintain the biomolecular recognition features of the native peptides and 3) emit fluorescence preferentially after target binding, improving signal-to-noise ratios for imaging. Furthermore, we have reported fluorogenic analogues with emission >600 nm to prepare of cyclic peptides for imaging tumor cells using multiphoton imaging in vivo.5 Recently, we have extended the toolbox with smaller amino acids, including phenylalanine-based fluorogenic building blocks for detection of urinary6 and ocular7 infections, the smallest turn-on fluorescent amino acids for peptide-PAINT imaging and super-resolution microscopy,8 and to fluorogenic tags for small proteins associated with immune cell function like interleukins, cyclophilins and chemokines.9 Finally, the talk will also briefly discuss our efforts to establish apply these fluorescent probes for clinical applications.

References

  1. Cheng, Z. et al. Nat. Rev. Chem. 2020, 4, 275.
  2. a) Mendive-Tapia, L. et. al. Nat. Commun. 2016, 7, 10940; b) Mendive-Tapia, L. et. al. Nat. Protoc. 2017, 12, 1588.
  3. a) Barth N. et al. Nat. Commun. 2020, 11, 4027; b) Kaplaneris, N. et al. Nat. Commun. 2021, 12, 3389.
  4. Scott, J. et al. Nat. Commun. 2022, 13, 2366.
  5. a) Subiros-Funosas, R. et. al. Chem. Sci. 2020, 11, 1368; b) Barth N. et al. Angew. Chem. Int. Ed. 2022, 61, e20211302; c) Cheng et al. Angew. Chem. Int. Ed. 2024, 63, e202404587.
  6. Mendive-Tapia et al. Angew. Chem. Int. Ed. 2022, 61, e202117218.
  7. Lochenie et al. Adv. Mat. 2024, 2404107.
  8. a) De Moliner et al. Angew. Chem. Int. Ed. 2023, 62, e202216231; b) Nestoros et al. Nat. Commun. 2024, 15, 7689.
  9. a) Reese et al. ACS Cent. Sci. 2024, 10, 143; b) Bertolini et al. ACS Cent. Sci. 2024, 10, 969; c) Kuru et al. Nat. Commun. 2024, 15, 7531; d) Bertolini et al. JACS 2024, 10, 30565.
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