Failure scenarios and the innovation cycle

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Sulfation of glycosaminoglycans and its Implications in human health and disorders

Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as cellâ cell and cellâ matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function, GAG sulfation patterns are referred to as the sulfation code. This review explores the role of GAG sulfation in different biological processes at the cell, tissue, and organism levels. We address the connection between the sulfation patterns of GAGs and several physiological processes and discuss the misregulation of GAG sulfation and its involvement in several genetic and metabolic disorders. Finally, we present the therapeutic potential of GAGs and their synthetic mimics in the biomedical field.info:eu-repo/semantics/publishedVersio

Synthesis and anticancer activity of silver(I)– N-heterocyclic carbene complexes derived from the natural xanthine products caffeine, theophylline and theobromine

A new library of silver(I)–N-heterocyclic carbene complexes prepared from the natural products caffeine, theophylline and theobromine is reported. The complexes have been fully characterised using a combi- nation of NMR spectroscopy, mass spectrometry, elemental analysis and X-ray diffraction analysis. Fur- thermore, the hydrophobicity of the complexes has been measured. The silver(I)–N-heterocyclic carbenes have been evaluated for their antiproliferative properties against a range of cancer cell lines of different histological types, and compared to cisplatin. The data shows different profiles of response when compared to cisplatin in the same panel of cells, indicating a different mechanism of action. Furthermore, it appears that the steric effect of the ligand and the hydrophobicity of the complex both play a role in the chemosensitivity of these compounds, with greater steric bulk and greater hydrophilicity delivering higher cytotoxicity