Evaluation of borinic acids as new, fast hydrogen peroxide–responsive triggers - Université Paris-Saclay
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2021

Evaluation of borinic acids as new, fast hydrogen peroxide–responsive triggers

Bogdan Iorga
Marie Erard

Résumé

Hydrogen peroxide (H 2 O 2 ) is responsible for numerous damages when overproduced, and its detection is crucial for a better understanding of H 2 O 2 -mediated signaling in physiological and pathological processes. For this purpose, various “off–on” small fluorescent probes relying on a boronate trigger have been prepared, and this design has also been involved in the development of H 2 O 2 -activated prodrugs or theranostic tools. However, this design suffers from slow kinetics, preventing activation by H 2 O 2 with a short response time. Therefore, faster H 2 O 2 -reactive groups are awaited. To address this issue, we have successfully developed and characterized a prototypic borinic-based fluorescent probe containing a coumarin scaffold. We determined its in vitro kinetic constants toward H 2 O 2 -promoted oxidation. We measured 1.9 × 10 4 m −1 ⋅s −1 as a second-order rate constant, which is 10,000-fold faster than its well-established boronic counterpart (1.8 m −1 ⋅s −1 ). This improved reactivity was also effective in a cellular context, rendering borinic acids an advantageous trigger for H 2 O 2 -mediated release of effectors such as fluorescent moieties.

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Blaise Gatin-Fraudet, Roxane Ottenwelter, Thomas Le Saux, Stéphanie Norsikian, Mathilde Pucher, et al.. Evaluation of borinic acids as new, fast hydrogen peroxide–responsive triggers. Proceedings of the National Academy of Sciences of the United States of America, 2021, 118 (50), pp.e2107503118. ⟨10.1073/pnas.2107503118⟩. ⟨hal-03542546⟩
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