Issue 5, 2021

Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling

Abstract

Fluorescent probes for biological imaging have revealed much about the functions of biomolecules in health and disease. Fluorogenic probes, which are fluorescent only upon a bioorthogonal reaction with a specific partner, are particularly advantageous as they ensure that fluorescent signals observed in biological imaging arise solely from the intended target. In this work, we report the first series of naphthalimide tetrazines for bioorthogonal fluorogenic labelling. We establish that all of these compounds can be used for imaging through photophysical, analytical and biological studies. The best candidate was Np6mTz, where the tetrazine ring is appended to the naphthalimide at its 6-position via a phenyl linker in a meta configuration. Taking our synthetic scaffold, we generated two targeted variants, LysoNpTz and MitoNpTz, which successfully localized within the lysosomes and mitochondria respectively, without the requirement of genetic modification. In addition, the naphthalimide tetrazine system was used for the no-wash imaging of insulin amyloid fibrils in vitro, providing a new method that can monitor their growth kinetics and morphology. Since our synthetic approach is simple and modular, these new naphthalimide tetrazines provide a novel scaffold for a range of bioorthogonal tetrazine-based imaging agents for selective staining and sensing of biomolecules.

Graphical abstract: Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling

Supplementary files

Article information

Article type
Paper
Submitted
10 Jun 2021
Accepted
24 Jun 2021
First published
05 Jul 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 1491-1498

Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling

M. E. Graziotto, L. D. Adair, A. Kaur, P. Vérité, S. R. Ball, M. Sunde, D. Jacquemin and E. J. New, RSC Chem. Biol., 2021, 2, 1491 DOI: 10.1039/D1CB00128K

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