期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 57, 期 39, 页码 12896-12900出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201807593
关键词
biosensors; cancer; DNA repair; fluorescent probes; nucleic acids
资金
- U.S. National Cancer Institute [R01 CA217809, R01 CA176611]
- California Tobacco-Related Disease Research Program [25IP-0020]
- City of Hope Comprehensive Cancer Center [P30 CA033572]
- NATIONAL CANCER INSTITUTE [P30CA033572, R01CA217809, R01CA176611] Funding Source: NIH RePORTER
The DNA repair enzyme ALKBH2 is implicated in both tumorigenesis as well as resistance to chemotherapy in certain cancers. It is currently under study as a potential diagnostic marker and has been proposed as a therapeutic target. To date, however, there exist no direct methods for measuring the repair activity of ALKBH2 invitro or in biological samples. Herein, we report a highly specific, fluorogenic probe design based on an oligonucleotide scaffold that reports directly on ALKBH2 activity both invitro and in cell lysates. Importantly, the probe enables the monitoring of cellular regulation of ALKBH2 activity in response to treatment with the chemotherapy drug temozolomide through a simple fluorescence assay, which has only previously been observed through indirect means such as qPCR and western blots. Furthermore, the probe provides a viable high-throughput assay for drug discovery.
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