Our research focuses on the investigation of the chemical, biophysical and structural properties of proteins, aiming at the deep understanding of their mode of action and with the long-term goal to exploiting the acquired knowledge to design and develop artificial molecules as positive or negative modulators of protein activity. In particular, we are interested in small regulatory proteins that play a role in cancer and vascular diseases.
Proteins are key biomolecules in many cellular processes including the activation of DNA transcription, the transport of messenger RNA from the nucleus to the cytoplasm, the biocatalysis of reactions (which otherwise would be slow and unspecific), the regulation of signaling cascades. Despite their diversity, all these processes share a fundamental mechanism, namely protein molecular recognition. Proteins may recognize themselves or other proteins as well as different classes of molecules (e.g. DNA, RNA, glycans) by means of specific non-covalent interactions such as hydrogen bonds, electrostatic and hydrophobic contacts. It is thus important to characterize the non-covalent network that allows biomole-cules exerting their function. This implies a deep sight into the structure and dynamics of proteins by using spectroscopic techniques (circular dichroism, fluorescence, nuclear magnetic resonance), which in some cases requires the use of chemically modified proteins.
Organic chemistry methods applied to proteins allow reproducing, mimicking and manipulating these very interesting biomolecules. For example, the preparation of proteins containing post-translational modifications (e.g. phosphorylation, acetylation, methylation, glycosylation) provides the tools to evaluate the structural and functional importance of these modifications that are essential to regulate the activity of proteins in the cells. Furthermore, the mimicry of protein interfaces by means of synthetic scaffolds leads to artificial, proteolitically stable modulators of protein-protein interactions, which are of significance for the development of drug-like molecules.