000165255 001__ 165255
000165255 005__ 20251219174252.0
000165255 0247_ $$2doi$$a10.1016/j.ijbiomac.2025.149435
000165255 0248_ $$2sideral$$a146990
000165255 037__ $$aART-2025-146990
000165255 041__ $$aeng
000165255 100__ $$aÁlvarez-Rodríguez, María Gabriela
000165255 245__ $$aEvaluating the therapeutic role of salvianolic acid A on pancreatic cancer cells through interaction with the intrinsically disordered protein NUPR1
000165255 260__ $$c2025
000165255 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165255 5203_ $$aThe nuclear protein 1 (NUPR1) is an intrinsically disordered protein (IDP) involved in stress processes in the cell. We have been developing, by using organic chemistry, several small molecules which hamper in vitro and in cell-based assays NUPR1 biomolecular interactions by targeting its two hot-spots around Ala33 and Thr68. In this work, we used a natural compound, salvianolic acid A (SAA), to target NUPR1. SAA has anti-cancer and anti-inflammatory properties. Binding in vitro was monitored by using fluorescence, isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR); the affinity was in the low micromolar range, as shown by fluorescence and ITC. The NMR spectra of NUPR1, in the absence and in the presence of SAA, indicated that binding involved several polypeptide patches of NUPR1, as well as its hot-spots; however, the binding did not alter the disordered nature of the protein. Moreover, molecular docking simulations provided a model of the binding at the atomic level. Results of proliferation cellular assays with MIA PaCa-2 cells indicated that the IC50 was ~20 μM, confirming the affinity values found by fluorescence and ITC. SAA was also capable of inhibiting the formation of stress granules (SGs) triggered by NUPR1. Our work shows that a plant-derived molecule can target an IDP involved in cancer, with affinities in the low micromolar range. Our model compound can hamper the pathological state (SG formation) triggered by this IDP, and indicates that the search for potential inhibitors of disordered proteins could be further extended to bioactive natural compounds.
000165255 536__ $$9info:eu-repo/grantAgreement/EC/H2020/CL6-2024/EU/Circular economy and bioeconomy sectors/CIRCBIO-01/101181841$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 CL6-2024-CIRCBIO-01/101181841
000165255 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000165255 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000165255 700__ $$aEstaras, Matías
000165255 700__ $$aHornos, Felipe
000165255 700__ $$aRizzuti, Bruno
000165255 700__ $$aSantofimia-Castaño, Patricia
000165255 700__ $$aIovanna, Juan L.
000165255 700__ $$aNeira, José L.
000165255 773__ $$g337 (2025), 149435 [11 pp.]$$pInt. j. biol. macromol.$$tInternational journal of biological macromolecules$$x0141-8130
000165255 8564_ $$s2600613$$uhttps://zaguan.unizar.es/record/165255/files/texto_completo.pdf$$yVersión publicada
000165255 8564_ $$s2633700$$uhttps://zaguan.unizar.es/record/165255/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000165255 909CO $$ooai:zaguan.unizar.es:165255$$particulos$$pdriver
000165255 951__ $$a2025-12-19-14:43:53
000165255 980__ $$aARTICLE