Abstract
Affinity-based protein profiling has proven to be a powerful method in target identification of bioactive molecules. Here, this technology was applied in two photoreactive anticancer inhibitors, arenobufagin and HM30181. Using UV irradiation, these photoreactive reagents can covalently cross-link to target proteins, leading to a covalent binding with target proteins. Moreover, the cellular on/off targets of these two molecules, including ATP1A1, MDR1, PARP1, DDX5, NOP2, RAB6A, and ERGIC1 were first identified by affinity-based protein profiling and bioimaging approaches. The protein hit, PARP1, was further validated to be involved in the function of the anticancer effects.
| Original language | English |
|---|---|
| Pages (from-to) | 2546-2552 |
| Number of pages | 7 |
| Journal | ACS Chemical Biology |
| Volume | 14 |
| Issue number | 12 |
| Online published | 19 Nov 2019 |
| DOIs | |
| Publication status | Published - 20 Dec 2019 |
| Externally published | Yes |
Funding
Funding was provided by National Natural Science Foundation of China (81803389, 21602079, 21877050), Science and Technology Program of Guangdong Province (2017A050506028, 2019B151502025), Science and Technology Program of Guangzhou (201704030060, 201805010007), China Postdoctoral Science Foundation (No.2017M622923), and the Ph.D. Start-up Fund of Natural Science Foundation of Guangdong Province, China (NO. 2018A030310651). We thank S. Q Yao (NUS, Singapore) for the invaluable suggestions and support on this work.
Research Keywords
- PHOTO-CROSS-LINKERS
- PHOTOAFFINITY PROBES
- TOAD VENOM
- CANCER
- BUFADIENOLIDE
- ARENOBUFAGIN
- HM30181
- DESIGN
