Modular Design and Scaffold-Synthesis of Multi-Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis

Li, Y.; Wang, C.; Wang, H.; Sun, K.; Lu, S.; Wang, Y.; Zhang, L.; Jing, S.; Cordes, T.

doi:10.1101/2024.05.24.595706

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bioRxiv · 10.1101/2024.05.24.595706

Modular Design and Scaffold-Synthesis of Multi-Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis

Li, Y.·Wang, C.·Wang, H.·Sun, K.·Lu, S.·Wang, Y.·Zhang, L.·Jing, S.·Cordes, T.

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Abstract

Modified commercial fluorophores are essential tools for optical imaging and biomedical research. Their synthetic modification to incorporate new functions, however, remains a challenging task. Conventional strategies rely on linear synthesis in which a parent framework is gradually extended. We here designed and synthesized a versatile library of functional fluorophores via a scaffold-based Ugi four-component reaction (U-4CR). The adaptability of the scaffold is achieved through modification of starting materials. This allows to use a small range of starting materials for the creation of fluorogenic probes that can detect reactive-oxygen species and where the localization into subcellular organelles or membranes can be controlled. We present reaction yields ranging from 60% to 90% and discovered that some compounds can even function as imaging and therapeutic agents via Fenton chemistry inducing pyroptosis in living cancer cells. Our study underlines the potential of scaffold-based synthesis for versatile creation of functional fluorophores and their applications.

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Li, Y., Wang, C., Wang, H., Sun, K., Lu, S., Wang, Y., Zhang, L., Jing, S., Cordes, T.. 2024-05-27. Modular Design and Scaffold-Synthesis of Multi-Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis. https://doi.org/10.1101/2024.05.24.595706

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