Targeting Galectins With Glycomimetics.

Among glycan-binding proteins, galectins, ß-galactoside-binding lectins, exhibit relevant biological roles and are implicated in many diseases, such as cancer and inflammation. Their involvement in crucial pathologies makes them interesting targets for drug discovery. In this review, we gather the last approaches toward the specific design of glycomimetics as potential drugs against galectins. Different approaches, either using specific glycomimetic molecules decorated with key functional groups or employing multivalent presentations of lactose and N-acetyl lactosamine analogs, have provided promising results for binding and modulating different galectins. The review highlights the results obtained with these approximations, from the employment of S-glycosyl compounds to peptidomimetics and multivalent glycopolymers, mostly employed to recognize and/or detect hGal-1 and hGal-3.

bioNMR-based identification of natural anti-Aß compounds in Peucedanum ostruthium.

The growing interest in medicinal plants for the identification of new bioactive compounds and the formulation of new nutraceuticals and drugs prompted us to develop a powerful experimental approach allowing the detailed metabolic profiling of complex plant extracts, the identification of ligands of macromolecular targets of biomedical relevance and a preliminary characterization of their biological activity. To this end, we selected Peucedanum ostruthium, a plant traditionally employed in Austria and Italy for its several potential therapeutic applications, as case study. We combined the use of NMR and UPLC-HR-MS for the identification of the metabolites present in its leaves and rhizome extracts. Due to the significant content of polyphenols, particularly chlorogenic acids, recently identified as anti-amyloidogenic compounds, polyphenols-enriched fractions were prepared and tested for their ability to prevent Aß1-42 peptide aggregation and neurotoxicity in a neuronal human cell line. STD-NMR experiments allowed the detailed identification of Aß oligomers' ligands responsible for the anti-amyloidogenic activity. These data provide experimental protocols and structural information suitable for the development of innovative molecular tools for prevention, therapy and diagnosis of Alzheimer's disease.