Pallara, ChiaraCabot, DéboraRivas, JosepBrun, SoniaSeco, JesúsAbuasaker, BaraaTarragó Clua, Maria TeresaJaumot i Pijoan, MontserratPrades, RogerAgell i Jané, Neus2022-10-242022-10-242022-09-222045-2322https://hdl.handle.net/2445/190110Oncogenic RAS proteins are important for driving tumour formation, and for maintenance of the transformed phenotype, and thus their relevance as a cancer therapeutic target is undeniable. We focused here on obtaining peptidomimetics, which have good pharmacological properties, to block Ras-effector interaction. Computational analysis was used to identify hot spots of RAS relevant for these interactions and to screen a library of peptidomimetics. Nine compounds were synthesized and assayed for their activity as RAS inhibitors in cultured cells. Most of them induced a reduction in ERK and AKT activation by EGF, a marker of RAS activity. The most potent inhibitor disrupted Raf and PI3K interaction with oncogenic KRAS, corroborating its mechanism of action as an inhibitor of protein-protein interactions, and thus validating our computational methodology. Most interestingly, improvement of one of the compounds allowed us to obtain a peptidomimetic that decreased the survival of pancreatic cancer cell lines harbouring oncogenic KRAS15 p.application/pdfengcc-by (c) Pallara, Chiara et al., 2022https://creativecommons.org/licenses/by/4.0/CàncerSíntesi de pèptidsProteïnes rasCàncer de pàncreesCancerPeptide synthesisRas proteinsPancreas cancerinfo:eu-repo/semantics/article7261012022-10-24info:eu-repo/semantics/openAccess933081436138080