To View Your Biomolecule, Click inside the Cell. (7th July 2021)

• Record Type: Journal Article
• Authors: Rigolot, Vincent; Biot, Christophe; Lion, Cedric
• Is Part Of: Angewandte Chemie. Volume 133:Number 43(2021)
• Page Start: 23268
• Page End: 23289
• Publication Date: 2021-07-07
• Subjects: bioimaging -- bioorthogonal chemistry -- chemical biology -- click chemistry -- intracellular labelling; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202101502
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The surging development of bioorthogonal chemistry has profoundly transformed chemical biology over the last two decades. Involving chemical partners that specifically react together in highly complex biological fluids, this branch of chemistry now allows researchers to probe biomolecules in their natural habitat through metabolic labelling technologies. Chemical reporter strategies include metabolic glycan labelling, site‐specific incorporation of unnatural amino acids in proteins, and post‐synthetic labelling of nucleic acids. While a majority of literature reports mark cell‐surface exposed targets, implementing bioorthogonal ligations in the interior of cells constitutes a more challenging task. Owing to limiting factors such as membrane permeability of reagents, fluorescence background due to hydrophobic interactions and off‐target covalent binding, and suboptimal balance between reactivity and stability of the designed molecular reporters and probes, these strategies need mindful planning to achieve success. In this review, we discuss the hurdles encountered when targeting biomolecules localized in cell organelles and give an easily accessible summary of the strategies at hand for imaging intracellular targets. Abstract : Recent advances in biorthogonal click chemistry have broadened the scope of bioimaging and bioanalytical studies applied to a large array of molecular targets in vivo as well as ex vivo. Here, we discuss the hurdles encountered when targeting intracellular compartments by metabolic labeling and other approaches, and present the solutions currently being developed to improve the efficiency of click ligations in living cells.