Synthesis of Uronic Acid 1-Azasugars as Putative Inhibitors of α-Iduronidase, β-Glucuronidase and Heparanase**

1-Azasugar analogues of l -iduronic acid (l -IdoA) and d -glucuronic acid (d -GlcA) and their corresponding enantiomers have been synthesized as potential pharmacological chaperones for mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by mutations in the gene encoding α-iduronidase (IDUA). The compounds were efficiently synthesized in nine or ten steps from d - or l -arabinose, and the structures were confirmed by X-ray crystallographic analysis of key intermediates. All compounds were inactive against IDUA, although l -IdoA-configured 8 moderately inhibited β-glucuronidase (β-GLU). The d -GlcA-configured 9 was a potent inhibitor of β-GLU and a moderate inhibitor of the endo-β-glucuronidase heparanase. Co-crystallization of 9 with heparanase revealed that the endocyclic nitrogen of 9 forms close interactions with both the catalytic acid and catalytic nucleophile.     

A Laser Synthesis Route to Boron-Doped Gold Nanoparticles Designed for X-Ray Radiotherapy and Boron Neutron Capture Therapy Assisted by CT Imaging

New multifunctional theranostic vectors allow the expansion of cancer therapeutic approaches toward scarcely investigated fields. One example is the combination of boron neutron capture therapy (BNCT) and X-ray radiotherapy (XRT) for treating normal and XRT-resistant hypoxic tumor regions and reduce recurrence. Of great relevance for BNCT is also the support of viable, rapid, safe, and reliable techniques for the localization and quantification of the radiosensitizers in the tissues. To address these challenges, polymer-coated Au-B nanoparticles (NPs) are obtained starting from a laser ablation in liquid process. Despite thermodynamic constraints, the two elements coexist by short-range boron segregation in the gold lattice, as demonstrated experimentally and explained with the support of density functional theory calculations. Thus, the Au-B NPs maintain a marked gold character such as biocompatibility, stability, and straightforward surface chemistry with thiolated compounds, desirable for the integration with agents capable of cell targeting and internalization. Overall, the Au-B NPs exhibit the appropriate features for the investigation of combined BNCT and XRT, supported by the localization and quantification with X-ray computed tomography imaging. Besides, the Au-B nanotechnology tool is achievable without renouncing to reproducibility, environmental sustainability, and cost affordability thanks to the laser-assisted synthetic pathway.     

Recyclability Studies on Poly(lactic acid)/Poly(butylene succinate-co-adipate) (PLA/PBSA) Biobased and Biodegradable Films

Poly(lactic acid)/poly(butylene succinate-co-adipate) (PLA/PBSA) blends are found promising for film packaging applications because of their flexibility, resistance, and compostability. Industrially extruded granules and films based on PLA and containing different amounts of PBSA are reprocessed through mini-extrusion, to simulate recycling, and tested in terms of their melt flow rate as a function of PBSA content. Moreover, pure PLA commercial granules and the film produced extruding the PLA/PBSA 60/40 blend are reprocessed several times by injection molding and characterized in terms of melt flow rate, mechanical properties, thermal properties, and color as a function of injection molding cycles. The variation in melt fluidity and thermo-mechanical properties is negligible up to 3 injection molding cycles for both pure PLA granules and PLA/PBSA blend. In the case of blend the change in color (yellowing and darkening) is more evident and slight local compositional change in injection molded items can be evidenced as well as a slight decrease in PBS crystallinity as a function of injection molding cycles. Nevertheless, in applications where these aspects are not critical, these materials can be recycled by extrusion or injection molding before being composted, thus prolonging their life cycle and storing carbon in them as longer as possible.     

Advances in Synthetic Biology of Fungi and Contributions to the Discovery of New Molecules

The sequencing of fungal genomes is becoming increasingly accessible, with a wealth of data already available. In parallel, the prediction of the putative biosynthetic pathways responsible for the synthesis of potential new natural products is also increasing. The difficulty of translating computational analyses into available compounds is becoming evident, slowing down a process that was thought to be faster with the advent of the genomic era. Advances in gene techniques made it possible to genetically modify a wider range of organisms, including fungi typically considered recalcitrant to DNA manipulation. However, the possibility of screening many gene cluster products for new activities in a high-throughput manner remains unfeasible. Nonetheless, some updates on the synthetic biology of fungi could provide interesting insights that could help to achieve this goal in the future.