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Projeto de investigação
Rendering 3D images with attributes learned from 2D images via Deep Learning
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Developing arylamide foldamers as new platforms for glycan microarray technology
Publication . Pinheiro, Gonçalo Manuel Silva de Almeida; Mateus, Pedro; Palma, Angelina
Glycan microarrays are powerful tools for investigating the carbohydrate-binding specificity of proteins and antibodies, identifying potential drug targets, and detecting biomarkers that may indicate disease states. These arrays typically feature glycan sequences attached to a surface using a linker at the glycan’s reducing end. However, the spatial arrangement of glycans on a cell surface differs significantly from that on a synthetic glycoarray. Glycoconjugate mimetics, which position glycans similarly to natural glycoproteins, can be integrated into arrays to create a more physiologically relevant platform for probing glycan-binding proteins. However, few allow precise control over the number, orientation, and distance between glycans.
This project aimed to design and synthesized arylamide foldamers—oligomers containing aromatic amide segments—as a new platform for the multivalent display of carbohydrates, suitable for integration with current microarray technology platforms. The key features of arylamide foldamers are expected to offer distinct advantages, as the densities and orientations of glycan ligands are dictated by their structure rather than the unclear characteristics of conventional glycan arrays.
To provide proof-of-principle, a sequence of five monomers was designed to form a single-strand helix spanning two turns, featuring an alkyne side chain to enable the conjugation of an α-mannose ligand or a fluorophore via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), along with a free amine group to allow covalent immobilization onto NHS-activated glass slides.
To prepare the envisioned compounds, it was first necessary to synthesize the respective monomer units—two based on published methods and three of new design—as well as rhodamine B and α-mannose featuring azide-terminated linkers. The foldamer conjugates were then assembled through solid-phase synthesis, followed by CuAAC click chemistry.
The work described in this dissertation represents the initial steps toward the integration of glycofoldamers into microarray technology and will serve as a foundation for future advancements.
N-heterocyclic carbene iron complexes as anticancer agents
Publication . Lenis-Rojas, Oscar A.; Cordeiro, Sandra; Horta-Meireles, Marta; Fernández, Jhonathan Angel Araujo; Vila, Sabela Fernández; Rubiolo, Juan Andrés; Cabezas-Sainz, Pablo; Sanchez, Laura; Fernandes, Alexandra R.; Royo, Beatriz; Instituto de Tecnologia Química e Biológica António Xavier (ITQB); DCV - Departamento de Ciências da Vida; UCIBIO - Applied Molecular Biosciences Unit; MDPI - Multidisciplinary Digital Publishing Institute
Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.
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Entidade financiadora
European Commission
Programa de financiamento
H2020
Número da atribuição
101022162