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.
Department of Chemistry and Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, California, USA.
Ellen M
EM
Sletten
Carolyn R
CR
Bertozzi
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