Open AccessHOPPI-NMR: Hot-Peptide-Based Screening Assay for Inhibitors of Protein–Protein Interactions by NMR
Author(s) -
Diego Brancaccio,
Salvatore Di Maro,
Linda Cerofolini,
Stefano Giuntini,
Marco Fragai,
Claudio Luchinat,
Stefano Tomassi,
Antonio Limatola,
Pasquale Russomanno,
Francesco Merlino,
Ettore Novellino,
Alfonso Carotenuto
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00620
Subject(s) - computational biology , drug discovery , chemistry , protein–protein interaction , peptide , combinatorial chemistry , biochemistry , biology
Protein-protein interactions (PPIs) contribute to the onset and/or progression of several diseases, especially cancer, and this discovery has paved the way for considering disruption of the PPIs as an attractive anti-tumor strategy. In this regard, simple and efficient biophysical methods for detecting the interaction of the inhibitors with the protein counterpart are still in high demand. Herein, we describe a convenient NMR method for the screening of putative PPI inhibitors based on the use of "hot peptides" (HOPPI-NMR). As a case study, HOPPI-NMR was successful applied to the well-known p53/MDM2 system. Our outcomes highlight the main advantages of the method, including the use of a small amount of unlabeled proteins, the minimization of the risk of protein aggregation, and the ability to identify weak binders. The last leaves open the possibility for application of HOPPI-NMR in tandem with fragment-based drug discovery as a valid strategy for the identification of novel chemotypes acting as PPI inhibitors.