Teaching staff

Main research interests are in the field of organic and bioorganic chemistry. Focus of the first research line is on the design, synthesis, and characterization of novel and modulable integrin-targeted RGD-based pseudopeptide ligands and their covalent conjugates with active units. These platforms are intended for molecular recognition studies and biomedical applications in the field of targeted anti-cancer therapy and non-invasive diagnosis. Integrins are cell surface receptors playing essential roles in many physiological and pathological events. The relevance of RGD-dependent alphaVbeta3, alphaVbeta5, alphaVbeta6 and alpha5beta1 integrins during tumour angiogenesis and tumour development, inflammation and fibrosis is well established. Furthermore, differential integrin expression patterns in normal versus tumour tissue as well as in different stages of tumour progression make these receptors as valuable disease biomarker. In recent years our efforts in the area of specific integrin ligands led to the development of a new series of gamma-aminocyclopentanecarboxylic acid (Acpca)-based or gamma-aminoproline (Amp)-based RGD-cyclopeptides which turned out to be very potent alphaVbeta3 alphaVbeta5, alphaVbeta6 and alpha5beta1 integrin binders with IC50 binding affinities in the nanomolar range. In particular, the covalent conjugation of our AmpRGD ligands with cytotoxic agents or diagnostic probes such as fluorescent probes or metal-chelating units (e.g. DOTA), as well as their embodiment in liposomal nanoparticles were accomplished and biological properties of these bioconjugates were evaluated with notable results. Focus of the second research line is the development of new methodologies for asymmetric synthesis merging selectivity and molecular diversity. In this field major efforts have been devoted to the design and synthesis of novel multi-site (pro)nucleophilic and (pro)electrophilic carbon matrices – mainly in the heterocyclic domain – and their exploitation in vinylogous and multivinylogous carbon-carbon bond-forming reactions. In recent past years, application of the vinylogy concept in asymmetric synthesis enabled us to access diverse collections of high-quality small-molecule scaffolds including unnatural and natural carbasugars, alkaloids, nucleosides, amino acids, peptidomimetics and heterocycle matrices such as butenolides, pyrrolinones, 2-oxindoles. Thus, the exploitation of the “vinylogy concept” represents a powerful opportunity to selectively access molecular diversity in the search of biologically and pharmaceutically relevant molecules.