Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling,RSC Chemical Biology

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Versatile naphthalimide tetrazines for fluorogenic bioorthogonal labelling
RSC Chemical Biology ( IF 4.2 ) Pub Date : 2021-07-05 , DOI: 10.1039/d1cb00128k
Marcus E Graziotto _{1,

2} , Liam D Adair _{1,

2} , Amandeep Kaur _{3,

4} , Pauline Vérité ₅ , Sarah R Ball ₃ , Margaret Sunde _{3,

4} , Denis Jacquemin ₅ , Elizabeth J New _{1,

2,

4}

Affiliation

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.

中文翻译：

用于荧光生物正交标记的多功能萘酰亚胺四嗪

用于生物成像的荧光探针揭示了生物分子在健康和疾病中的功能。荧光探针仅在与特定伙伴发生生物正交反应时才发出荧光，因此特别有利，因为它们确保生物成像中观察到的荧光信号仅来自预期目标。在这项工作中，我们报告了第一个用于生物正交荧光标记的萘酰亚胺四嗪系列。我们确定所有这些化合物都可以通过光物理、分析和生物学研究用于成像。最好的候选者是Np6mTz ，其中四嗪环通过间位构型的苯基连接体附加到萘二甲酰亚胺的 6 位上。利用我们的合成支架，我们生成了两个靶向变体LysoNpTz和MitoNpTz，它们分别成功地定位在溶酶体和线粒体内，而不需要进行遗传修饰。此外，萘酰亚胺四嗪系统用于胰岛素淀粉样原纤维的体外免洗成像，为监测其生长动力学和形态提供了一种新方法。由于我们的合成方法简单且模块化，这些新型萘酰亚胺四嗪为一系列基于生物正交四嗪的成像剂提供了一种新颖的支架，用于生物分子的选择性染色和传感。

更新日期：2021-07-05

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