Small organic molecules and proteins: a journey through bioactive compounds, receptors and biocatalysis

Herein, the research activity I carried out during my PhD is reported, comprising several projects ranging from organic synthesis to protein chemistry with the common aim of studying the design, synthesis and application of bioactive compounds in health. The projects are grouped into three macro areas. The first one is focused on bioactive β-lactam-based compounds, starting from the synthesis and characterization of a small library of new ligands designed for leukocyte integrins. Then, the application of β-lactam integrin agonists in different drug delivery systems is described, starting from poly-L-lactic acid-based biomaterials loaded with an α4β1 integrin agonist, able to help wound healing in diabetic mice. Then, Targeted Drug Delivery Systems where the integrin agonist acts as the targeting unit, implemented with an imaging portion for theranostics, are depicted. A new methodology for the synthesis of bioactive N-sulfenyl β-lactam compounds starting from new N-halo azetidin-2-ones and TEMPO is also described in this section. Moving toward proteins, another macro area of this thesis is dedicated to biocatalysis, by dealing with laccases, multicopper oxidases which carry out greener oxidation reactions using oxygen as the oxidant and producing water as the only co-product. The immobilization of laccase from Trametes versicolor into PLLA scaffolds by emulsion electrospinning and the application of this heterogenous catalyst in Laccase-Mediator-System (LMS) oxidations of alcohols and amines is investigated. The effect of the introduction of visible light irradiation in LMS oxidation reactions is also described here. In the final area of the thesis, the work I carried out during six months in the group of Prof. Jesús Jiménez-Barbero at CICbioGUNE (Spain) is reported. This final chapter will merge the world of small compounds and proteins by describing the use of NMR methodologies to study ligand-protein interactions, focusing on I-branched glycans and some galectins as their lectin receptors.