Second-generation difluorinated cyclooctynes for copper-free click chemistry.
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.
Codelli
Julian A
JA
Departments of Chemistry, University of California, Berkeley, California 94720, USA.
Baskin
Jeremy M
JM
Agard
Nicholas J
NJ
Bertozzi
Carolyn R
CR
D000480:Alkynes / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D002384:Catalysis; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D003500:Cyclization; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D006844:Hydrocarbons, Cyclic / Q000737:chemistry* / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry* / Q000378:metabolism; D019169:Jurkat Cells; D007700:Kinetics; D011134:Polysaccharides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D013194:Staining and Labeling
D000480:Alkynes; D001386:Azides; D006844:Hydrocarbons, Cyclic; D006845:Hydrocarbons, Fluorinated; D011134:Polysaccharides; D003300:Copper; D016650:Fluorescein-5-isothiocyanate