期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 53, 期 43, 页码 11473-11477出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201405233
关键词
activity-based probes; mass cytometry; multiparameter analysis; organotellurium compounds; tumor hypoxia
资金
- Natural Science and Engineering Research Council (NSERC), DVS Sciences
- Canadian Cancer Society [702397]
Mass cytometry (MC) offers unparalleled potential for the development of highly parameterized assays for characterization of single cells within heterogeneous populations. Current reagents compatible with MC analysis employ antibody-metal-chelating polymer conjugates to report on the presence of biomarkers. Here, we expand the utility of MC by developing the first activity-based probe designed specifically for use with the technology. A compact MC-detectable telluroether is linked to a bioreductively sensitive 2-nitroimidazole scaffold, thereby generating a probe sensitive to cellular hypoxia. The probe exhibits low toxicity and is able to selectively label O-2-deprived cells. A proof-of-concept experiment employing metal-bound DNA intercalators demonstrates that a heterogeneous mixture of cells with differential exposure to O-2 can be effectively discriminated by the quantity of tellurium-labeling. The organotellurium reagents described herein provide a general approach to the development of a large toolkit of MC-compatible probes for activity-based profiling of single cells.
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