Relatório de Pós-Doutorado
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- ItemLigand screening of RNA binding proteins acting as potential disease targets in cancer and neurology by weak affinity chromatography(Universidade Estadual de Campinas (UNICAMP), 2022) Amaral, Bruno Sérgio do; Massirer, Katlin B.The Bicaudal C homolog 1 (BICC1) have been identified in more than 250 organisms. Structurally, BICC1 presents three KH domains and a SAM domain, responsible to RNA-binding and protein-protein interactions, respectively. In human, BICC1 were related with kidney dysplasia and associated with depression. Thus, BICC1 constitute an important biological target for drug development. With the aim of expanding the druggable proteome and suggest small molecules to be used as chemical starting points for mapping the protein chemical space and for leading to inhibitors, we proposed to carry out fragment-based drug discovery (FBDD) by weak affinity chromatography coupled to mass spectrometry (WAC-MS). Thus, BICC was immobilized on silica support and used as a stationary phase in capillary columns. According to this strategy, a fragment library composed by 1534 chemical fragments were screened and characterized the potential hits by the affinity constants (KD).