RT Journal Article
T1 Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide
A1 Learte Aymamí, Soraya
A1 Martin-Malpartida, Pau
A1 Roldán-Martín, Lorena
A1 Sciortino, Giuseppe
A1 Couceiro, José R.
A1 Maréchal, Jean-Didier
A1 Macias, Maria J
A1 Mascareñas Cid, José Luis
A1 Vázquez Sentís, Marco Eugenio
AB RAS oncoproteins are molecular switches associated with critical signaling pathways that regulate cell proliferation and differentiation. Mutations in the RAS family, mainly in the KRAS isoform, are responsible for some of the deadliest cancers, which has made this protein a major target in biomedical research. Here we demonstrate that a designed bis-histidine peptide derived from the αH helix of the cofactor SOS1 binds to KRAS with high affinity upon coordination to Pd(II). NMR spectroscopy and MD studies demonstrate that Pd(II) has a nucleating effect that facilitates the access to the bioactive α-helical conformation. The binding can be suppressed by an external metal chelator and recovered again by the addition of more Pd(II), making this system the first switchable KRAS binder, and demonstrates that folding-upon-binding mechanisms can operate in metal-nucleated peptides. In vitro experiments show that the metallopeptide can efficiently internalize into living cells and inhibit the MAPK kinase cascade
PB Springer Nature
PB Macmillan Publishers Ltd
SN 2399-3669
YR 2022
FD 2022
LK http://hdl.handle.net/10347/28863
UL http://hdl.handle.net/10347/28863
LA eng
NO Learte-Aymamí, S.; Martin-Malpartida, P.; Roldán-Martín, L.; Sciortino, G. ; Couceiro, J. R. ; Maréchal, J.-D.; Macias, M. J.; Mascareñas, J. L.; Vázquez, M. E. (2022), Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide. Commun. Chem., 5: 75. doi: 10.1038/s42004-022-00691-7
DS Minerva
RD 23 abr 2026