Biocompatible copper(I) catalysts for in vivo imaging of glycans.
The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is the standard method for bioorthogonal conjugation. However, current Cu(I) catalyst formulations are toxic, hindering their use in living systems. Here we report that BTTES, a tris(triazolylmethyl)amine-based ligand for Cu(I), promotes the cycloaddition reaction rapidly in living systems without apparent toxicity. This catalyst allows, for the first time, noninvasive imaging of fucosylated glycans during zebrafish early embryogenesis. We microinjected embryos with alkyne-bearing GDP-fucose at the one-cell stage and detected the metabolically incorporated unnatural sugars using the biocompatible click chemistry. Labeled glycans could be imaged in the enveloping layer of zebrafish embryos between blastula and early larval stages. This new method paves the way for rapid, noninvasive imaging of biomolecules in living organisms.
Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Ave, Bronx, New York 10461, United States.
David
D
Soriano Del Amo
Wei
W
Wang
Hao
H
Jiang
Christen
C
Besanceney
Amy C
AC
Yan
Matthew
M
Levy
Yi
Y
Liu
Florence L
FL
Marlow
Peng
P
Wu
D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry* / Q000633:toxicity; D036703:Blastula / Q000378:metabolism; D002384:Catalysis; D002460:Cell Line; D002470:Cell Survival; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry*; D047108:Embryonic Development; D005643:Fucose / Q000378:metabolism; D006801:Humans; D008845:Microinjections; D057054:Molecular Imaging / Q000379:methods*; D011134:Polysaccharides / Q000378:metabolism*; D013997:Time Factors; D014230:Triazoles / Q000737:chemistry; D015027:Zebrafish / Q000196:embryology
D000480:Alkynes; D001386:Azides; D001672:Biocompatible Materials; D011134:Polysaccharides; D014230:Triazoles; D005643:Fucose; D003300:Copper