Competitive Metabolite Profiling of Natural Products Reveals Subunit Specific Inhibitors of the 20S Proteasome
| Type of Publication: | Journal article |
| Publication status: | Published |
| URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-2-2erpbpd9qo5z1 |
| Author: | Pawar, Atul; Basler, Michael; Goebel, Heike; Alvarez Salinas, Gerardo Omar; Groettrup, Marcus; Böttcher, Thomas |
| Year of publication: | 2020 |
| Published in: | ACS Central Science ; 6 (2020), 2. - pp. 241-246. - American Chemical Society (ACS). - ISSN 2374-7943. - eISSN 2374-7951 |
| DOI (citable link): | https://dx.doi.org/10.1021/acscentsci.9b01170 |
| Summary: |
We have developed a syringolin-based chemical probe and explored its utility for the profiling of metabolite extracts as potent inhibitors of the 20S proteasome. Activity-guided fractionation by competitive labeling allowed us to isolate and identify glidobactin A and C as well as luminmycin A from a Burkholderiales strain. The natural products exhibited unique subunit specificities for the proteolytic subunits of human and mouse constitutive and immunoproteasome in the lower nanomolar range. In particular, glidobactin C displayed an unprecedented β2/β5 coinhibition profile with single-digit nanomolar potency in combination with sufficiently high cell permeability. These properties render glidobactin C a promising live cell proteasome inhibitor with potent activity against human breast cancer cell lines and comparably low immunotoxicity.
|
| Subject (DDC): | 540 Chemistry |
| Keywords: | Rodent models, Cells, Inhibitors, Peptides and proteins, Probes |
| Link to License: | In Copyright |
| Refereed: | Yes |
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PAWAR, Atul, Michael BASLER, Heike GOEBEL, Gerardo Omar ALVAREZ SALINAS, Marcus GROETTRUP, Thomas BÖTTCHER, 2020. Competitive Metabolite Profiling of Natural Products Reveals Subunit Specific Inhibitors of the 20S Proteasome. In: ACS Central Science. American Chemical Society (ACS). 6(2), pp. 241-246. ISSN 2374-7943. eISSN 2374-7951. Available under: doi: 10.1021/acscentsci.9b01170
@article{Pawar2020-02-26Compe-48520, title={Competitive Metabolite Profiling of Natural Products Reveals Subunit Specific Inhibitors of the 20S Proteasome}, year={2020}, doi={10.1021/acscentsci.9b01170}, number={2}, volume={6}, issn={2374-7943}, journal={ACS Central Science}, pages={241--246}, author={Pawar, Atul and Basler, Michael and Goebel, Heike and Alvarez Salinas, Gerardo Omar and Groettrup, Marcus and Böttcher, Thomas} }
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