Gomes, Ana Sara, Helena Ramos, Sara Gomes, Joana B. Loureiro, Joana Soares, Valentina Barcherini, Paola Monti, Gilberto Fronza, Carla Oliveira, Lucília Domingues, Margarida Bastos, Daniel F. A. R. Dourado, Ana Luísa Carvalho, Maria João Romão, Benedita Pinheiro, Filipa Marcelo, Alexandra Carvalho, Maria M. M. Santos, and Lucília Saraiva. "
SLMP53-1 interacts with wild-type and mutant p53 DNA-binding domain and reactivates multiple hotspot mutations." 1864.1 (2020): 129440.
AbstractBackgroundHalf of human cancers harbour TP53 mutations that render p53 inactive as a tumor suppressor. As such, reactivation of mutant (mut)p53 through restoration of wild-type (wt)-like function represents one of the most promising therapeutic strategies in cancer treatment. Recently, we have reported the (S)-tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a new reactivator of wt and mutp53 R280K with in vitro and in vivo p53-dependent antitumor activity. The present work aimed a mechanistic elucidation of mutp53 reactivation by SLMP53-1.
Methods and results
By cellular thermal shift assay (CETSA), it is shown that SLMP53-1 induces wt and mutp53 R280K thermal stabilization, which is indicative of intermolecular interactions with these proteins. Accordingly, in silico studies of wt and mutp53 R280K DNA-binding domain with SLMP53-1 unveiled that the compound binds at the interface of the p53 homodimer with the DNA minor groove. Additionally, using yeast and p53-null tumor cells ectopically expressing distinct highly prevalent mutp53, the ability of SLMP53-1 to reactivate multiple mutp53 is evidenced.
Conclusions
SLMP53-1 is a p53-activating agent with the ability to directly target wt and a set of hotspot mutp53.
General Significance
This work reinforces the encouraging application of SLMP53-1 in the personalized treatment of cancer patients harboring distinct p53 status.
Viseu, F., and H. Rocha. "
Interdisciplinary technological approaches from a mathematics education point of view."
Science and mathematics education for 21st century citizens: challenges and ways forward. Eds. L. Leite, E. Oldham, A. Afonso, F. Viseu, L. Dourado, and H. Martinho. Nova Science Publishers, 2020.
AbstractMathematics has a strong presence in the school curriculum, often justified by its usefulness in social life, in the world of work and by its connections with other sciences. This interdisciplinary connection, in particular when it requires constructing and refining mathematical models and discussing their applications to solve problems of other sciences, can assist students to understand why mathematics is so important in school. In the development of interdisciplinary activities, the characteristics of the tasks emerge as an important aspect. The emphasis is on the use of technological materials and the way they can support the development of concepts, provide different representations and support deeper understandings, and offer a multifaceted support to collect data and simulate experiences. Based on these assumptions, the aim of this chapter is to present, analyse and discuss tasks that promote interdisciplinary technological approaches from a mathematical point of view. In this chapter we assume interdisciplinarity as a complex construct, and in order to clarify its meaning we will discuss several types of conceptions, from multidisciplinary, to interdisciplinary, and to transdisciplinary. We will then address related concepts, such as modelling and STEM, highlighting similarities and differences between them, to reach an understanding of interdisciplinarity. In the process of the interdiciplinary approach, digital technologies arise as a central element. Based on a set of tasks on mathematics and on different sciences, we discuss what can change on an interdisciplinary approach to the teaching and learning of mathematical content and on the articulation between subjects.
Outis, Mani, Vitor Rosa, César AT Laia, João Carlos Lima, Sónia Barroso, Ana Luísa Carvalho, Maria José Calhorda, and Teresa Avilés. "
Synthesis, Crystal Structure, and DFT Study of Two New Dinuclear Copper(I) Complexes Bearing Ar-BIAN Ligands Functionalized with NO2 Groups."
European Journal of Inorganic Chemistry. 2020 (2020): 2900-2911.
Abstract{Two new bis(aryl-imino)-acenaphthene, Ar-BIAN (Ar = 2