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Second-generation difluorinated cyclooctynes for copper-free click chemistry.

ABSTRACT: The 1,3-dipolar cycloaddition of azides and activated alkynes has been used for site-selective labeling of biomolecules in vitro and in vivo. While copper catalysis has been widely employed to activate terminal alkynes for [3 + 2] cycloaddition, this method, often termed "click chemistry", is currently incompatible with living systems because of the toxicity of the metal. We recently reported a difluorinated cyclooctyne (DIFO) reagent that rapidly reacts with azides in living cells without the need for copper catalysis. Here we report a novel class of DIFO reagents for copper-free click chemistry that are considerably more synthetically tractable. The new analogues maintained the same elevated rates of [3 + 2] cycloaddition as the parent compound and were used for imaging glycans on live cells. These second-generation DIFO reagents should expand the use of copper-free click chemistry in the hands of biologists.

SUBMITTER: Codelli JA

PROVIDER: S-EPMC2646667 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Second-generation difluorinated cyclooctynes for copper-free click chemistry.

Codelli Julian A JA Baskin Jeremy M JM Agard Nicholas J NJ Bertozzi Carolyn R CR

Journal of the American Chemical Society 20080805 34

The 1,3-dipolar cycloaddition of azides and activated alkynes has been used for site-selective labeling of biomolecules in vitro and in vivo. While copper catalysis has been widely employed to activate terminal alkynes for [3 + 2] cycloaddition, this method, often termed "click chemistry", is currently incompatible with living systems because of the toxicity of the metal. We recently reported a difluorinated cyclooctyne (DIFO) reagent that rapidly reacts with azides in living cells without the n ...[more]

PMID: 18680289

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