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http://hdl.handle.net/2445/190110
Title: | Peptidomimetics designed to bind to RAS effector domain are promising cancer therapeutic compounds. |
Author: | Pallara, Chiara Cabot, Débora Rivas, Josep Brun, Sonia Seco, Jesús Abuasaker, Baraa Tarragó Clua, Maria Teresa Jaumot i Pijoan, Montserrat Prades, Roger Agell i Jané, Neus |
Keywords: | Càncer Síntesi de pèptids Proteïnes ras Càncer de pàncrees Cancer Peptide synthesis Ras proteins Pancreas cancer |
Issue Date: | 22-Sep-2022 |
Publisher: | Nature Publishing Group |
Abstract: | Oncogenic 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 KRAS |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41598-022-19703-6 |
It is part of: | Scientific Reports, 2022, vol. 22, num. 12, p. 15810 |
URI: | http://hdl.handle.net/2445/190110 |
Related resource: | https://doi.org/10.1038/s41598-022-19703-6 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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