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. 2019 Oct 30;141(43):17048-17052.
doi: 10.1021/jacs.9b07193. Epub 2019 Sep 19.

"Close-to-Release": Spontaneous Bioorthogonal Uncaging Resulting from Ring-Closing Metathesis

Valerio Sabatino  1 , Johannes G Rebelein  1 , Thomas R Ward  1
Affiliations

"Close-to-Release": Spontaneous Bioorthogonal Uncaging Resulting from Ring-Closing Metathesis

Valerio Sabatino et al. J Am Chem Soc. .

Abstract

Bioorthogonal uncaging reactions offer versatile tools in chemical biology. In recent years, reactions have been developed to proceed efficiently under physiological conditions. We present herein an uncaging reaction that results from ring-closing metathesis (RCM). A caged molecule, tethered to a diolefinic substrate, is released via spontaneous 1,4-elimination following RCM. Using this strategy, which we term "close-to-release", we show that drugs and fluorescent probes are uncaged with fast rates, including in the presence of mammalian cells or in the periplasm of Escherichia coli. We envision that this tool may find applications in chemical biology, bioengineering and medicine.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Selected Biocompatible Uncaging Reactions
Scheme 2
Scheme 2. Functionalization of the Naphthalene Precursor 1 for the Spontaneous Release of Cargoes
See this image and copyright information in PMC

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