Covalent Peptide-Based N-Myc/Aurora-A Inhibitors Bearing Sulfonyl Fluoride Warheads.

ABSTRACT: Orthosteric inhibition of the N-Myc/Aurora-A protein-protein interaction (PPI) represents a potential mechanism by which degradation of N-Myc can be induced, given its interaction with Aurora-A competes with the factors that tag it for proteasomal degradation. As such, this would constitute an approach for the development of drugs to treat neuroblastoma, a childhood cancer that depends upon N-Myc. Reactive electrophiles have proven useful in the context of targeted covalent inhibitors, and in this work, we sought to improve the potency of a previously identified N-Myc-derived peptide by introducing a sulfonyl fluoride warhead. We successfully demonstrated selective labelling of Aurora-A using the resultant peptidomimetics and established this labelling as recognition-directed, providing va

SUBMITTER: Dawber RS 

PROVIDER: S-EPMC12867955 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature