Natural cyclic peptides have long served as a rich reservoir of bioactivity, occupying a unique region of the drug space that bridges the gap between small molecules and large biologics. Evolution has perfected the macrocyclic architecture to achieve exceptional target specificity and metabolic stability, providing a structural blueprint that allows these molecules to engage extended protein surfaces often inaccessible to conventional drugs. While early landmarks like cyclosporin A demonstrated the power of chameleonicity, the ability to adapt conformations to different environments - the field is currently undergoing a paradigm shift. Nature is no longer viewed merely as a source of lead compounds to be mined, but as a conceptual framework for de novo design. By integrating natural principles such as conformational constraint and amide-masking with cutting-edge technologies like mRNA display (e.g. RaPID) and artificial intelligence, researchers are now rationally engineering next-generation macrocycles, positioning them at the frontier of modern drug development.
Greta Bergamaschi, Giulia Lodigiani, Stefano Gandolfi et al.· Current Opinion in Chemical...· 0 citations
Microalgae are recognized as sustainable biofactories for metabolites relevant to nutraceutical, pharmaceutical, and marine drug applications. Nannochloropsis salina is notable for its production of bioactive lipids, including the pharmaceutically relevant omega-3 eicosapentaenoic acid (EPA). Here, we evaluated orange peel extract (OPE), a citrus by-product, as a substrate for mixotrophic cultivation of N. salina within a bioeconomy framework. OPE supplementation triggered dose-dependent physiological responses. Among the tested OPE concentrations, 5% supplementation resulted in the highest total fatty acid content, increasing fatty acids from 24.4% (control) to 30.6% and EPA from 6.4% to 9.8%, whereas 10% OPE maintained biomass pigmentation. Higher OPE levels enhanced antioxidant potential, raising total antioxidant capacity from 4.6 (control) to 6.7 mg/g vitamin C equivalents (with 10% OPE), while the highest concentrations induced metabolic stress, reducing biomass and altering lipid composition. Fourier transform infrared spectroscopy analyses revealed biochemical adjustments consistent with metabolic reorganization, including increased intensities of the amide I and II bands associated with protein-rich structures. Overall, OPE emerges as a cost-effective supplement capable of modulating the biochemical quality of N. salina while valorizing agro-industrial residues. The increases in EPA and antioxidant capacity support the potential of OPE-supplemented cultures as a platform for the production of marine-derived bioactive compounds.
Carlo Esposito, G. Aldini, Yanan Yin et al.· BioTech· 0 citations