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Probing the Small-Molecule Inhibition of an Anticancer Therapeutic Protein-Protein Interaction Using a Solid-State Nanopore.
- Source :
- Angewandte Chemie International Edition; 5/4/2016, Vol. 55 Issue 19, p5713-5717, 5p
- Publication Year :
- 2016
-
Abstract
- Nanopore sensing is an emerging technology for the single-molecule-based detection of various biomolecules. In this study, we probed the anticancer therapeutic p53 transactivation domain (p53TAD)/MDM2 interaction and its inhibition with a small-molecule MDM2 antagonist, Nutlin-3, using low-noise solid-state nanopores. Although the translocation of positively charged MDM2 through a nanopore was detected at the applied negative voltage, this MDM2 translocation was almost completely blocked upon formation of the MDM2/GST-p53TAD complex owing to charge conversion. In combination with NMR data, the nanopore measurements showed that the addition of Nutlin-3 rescued MDM2 translocation, indicating that Nutlin-3 disrupted the MDM2/GST-p53TAD complex, thereby releasing MDM2. Taken together, our results reveal that solid-state nanopores can be a valuable platform for the ultrasensitive, picomole-scale screening of small-molecule drugs against protein-protein interaction (PPI) targets. [ABSTRACT FROM AUTHOR]
- Subjects :
- NANOPORES
REMOTE sensing
BIOMOLECULES
ANTINEOPLASTIC agents
P53 antioncogene
Subjects
Details
- Language :
- English
- ISSN :
- 14337851
- Volume :
- 55
- Issue :
- 19
- Database :
- Complementary Index
- Journal :
- Angewandte Chemie International Edition
- Publication Type :
- Academic Journal
- Accession number :
- 114816536
- Full Text :
- https://doi.org/10.1002/anie.201511601