biostudies-literatureDawber RSMRC Discovery MedicineBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Councile70086https://www.ebi.ac.uk/biostudies/studies/S-EPMC12867955biostudies-literatureUnknown32(3)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 vaJournal of peptide science : an official publication of the European Peptide SocietyCovalent Peptide-Based N-Myc/Aurora-A Inhibitors Bearing Sulfonyl Fluoride Warheads.PMC12867955BB/V003577/1EP/V029169/1BB/V003577/2MR/N013840/1Wright MHBayliss RGimenez DWilson AJPreston GWWarriner SLDawber RSfalseCovalent Peptide-Based N-Myc/Aurora-A Inhibitors Bearing Sulfonyl Fluoride Warheads.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 va2026-01-01T00:00:00Z2026 Mar2026-07-15T06:37:34.935Z2026-07-02T03:08:38.759ZS-EPMC128679554163495410.1002/psc.70086