Two in a row!! A second publication in collaboration with Prof. E. Vázquez is also on-line


We are really glad to share this second 2022 collaborative paper, published at Commun. Chem., has been already accepted and it's available through the journal website. The communication is entitled "Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide" and authored by S. Learte-Aymamí, P. Martin-Malpartida, L. Roldán-Martín, G. Sciortino, J. R. Couceiro, J.-D. Maréchal, M. J. Macias, J. L. Mascareñas and M. E. Vázquez.

Abstract: 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.

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