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A brief description of our main research interests

 Design and synthesis of selective alpha-v-beta-3 and alpha-5-beta-1 integrin ligand conjugates as nanotheranostics for cancer cells detection and therapy

Weak protein-protein interactions are the widest occurring biological events regulating numerous functions. For this reason, the development of small molecules able to influence this network may afford useful tools for therapy and disclose information for the complete mapping of the interactome network. The group is interested in the interaction between integrins, transmembrane glycoproteins, and their extracellular matrix proteic partners. Due to the overexpression of alpha-v-beta-3 and alpha-5-beta-1  integrins on the surface of specific cancer cells, the design and synthesis of their ligands may be used to obtain delivery systems for cancer diagnosis and/or therapy. The design and synthesis of selective ligands has been already performed by mimicking the recognition sequence of integrin receptors, affording selective agonists and antagonist to these receptors. Now we are conjugating these small molecules to fluorescent tags, cytotoxic agents and nanoparticles with the aim to develop potential nanotheranostic tools and to understand integrin trafficking by means of fluorescent tracers.


Green Solid Phase Peptide Synthesis (SPPS) of oligopeptides for biological applications

Considering the increasing demand from the chemical and pharmaceutical markets for synthetic peptides, the attention to the optimization of SPPS protocols and their environmental impact is a relevant challenge. For instance, classic SPPS requires a large amount of solvent during the entire synthetic process and DMF is the most employed solvent, being however a highly reprotoxic solvent. The solvent has to efficiently assist the swelling of the resins, the couplings, the deprotections and the washings. A single solvent that is able to simultaneously afford optimal results during all these different steps may be difficult to find and for this reason a great number of green solvents are not suitable. Mixtures of different solvents showing efficient properties as swelling agents and solubilization media could represent novel successful tools, displaying better chemical/physical features than those exhibited by single components. The group is currently involved in the exploration of greener SPPS conditions and in the application of these novel approaches to pharmaceutical grade peptides.



 Novel stereoselective methods for linear and cyclic-beta-amino acid synthesis as building block for bioactive peptidomimetics

The synthesis of bioactive peptidomimetics requires the development of novel methodologies for the preparation of enantiopure building blocks. To this purpose, novel protocols involving biocatalysts, organocatalysts, organic electrochemistry and traditional organometallic catalysts are developed for the preparation of b-amino acids and five membered heterocycles. These fragments are introduced into peptidomimetic structures, with the aim to induce conformational restraints and to reduce sensitivity to proteases. Moreover, on the basis of the fundamental requirements for protein-protein interaction, the design and synthesis of peptidomimetic compounds based on heterocyclic scaffolds is realized by introducing linear or cyclic b-amino acids into oligopeptides, with the aim to increase resistance to enzymatic digestion.





Design and synthesis of selective alpha-4-beta-1 and beta-2 integrin ligands as therapeutic tools for inflammatory diseases

Neutrophils, activated in case of acute or chronic inflammation, overexpress a large number of receptor for recognition and migration to the site on injury. Among them alpha-4-beta-1 and beta-2 integrins have a fundamental role. The goal of the project is the design and synthesis of peptidomimetic ligands for the subclasses of receptors that are overexpressed on leukocytes. Moreover, the combined activity of bioactive synthetic ligands with other therapeutic tools, as for instance hyperbaric oxygen treatment, is studied to propose novel approaches for inflammatory diseases, non-healing ulcers and for fibromyalgia.