A hydrophilic azacyclooctyne for Cu-free click chemistry.
Biomolecules labeled with azides can be detected through Cu-free click chemistry with cyclooctyne probes, but their intrinsic hydrophobicity can compromise bioavailability. Here, we report the synthesis and evaluation of a novel azacyclooctyne, 6,7-dimethoxyazacyclooct-4-yne (DIMAC). Generated in nine steps from a glucose analogue, DIMAC reacted with azide-labeled proteins and cells similarly to cyclooctynes. However, its superior polarity and water solubility reduced nonspecific binding, thereby improving the sensitivity of azide detection.
Sletten
Ellen M
EM
Department of Chemistry and Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, California, USA.
Bertozzi
Carolyn R
CR
D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure
C530924:6,7-dimethoxyazacyclooct-4-yne; D001386:Azides; D005960:Glucosides; D006573:Heterocyclic Compounds, 1-Ring; C530926:methyl 6-bromoglucopyranoside; D001710:Biotin