Investigation of the biological activities of carbon-phosphorus and carbon-sulfur containing amino acids and of their derivatives, obtained by chemical synthesis and biocatalysis

Proponente Daniela De Biase - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Elisabetta Capuozzo Componenti strutturati del gruppo di ricerca
Alberto De Biase Componenti strutturati del gruppo di ricerca
Componente Qualifica Struttura Categoria
Alessandro Chinazzi tecnico Dipartimento di Fisiologia e Farmacologia "Vittorio Erspamer" Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca
Laura Onillon studentessa borsista Université d'Angers (France) Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca
Fabio Giovannercole borsista Istituto Pasteur Fondazione Cenci Bolognetti Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca

This project frames into the quest for antibiotics with novel scaffolds and mechanism of action, and for novel compounds with anti-inflammatory and anti-oxidative activity. We will evaluate the biological properties of compounds that include analogues/derivatives of L-glutamate, L-cysteine and L-homocysteine.
The mechanism through which C-P-containing compounds, patented as antibiotics, exert their activity still needs to be elucidated. We will give a contribution in this direction.
The C-S containing compounds will be tested for anti-inflammatory, anti-oxidative and antiangiogenic activities. Some of these compounds include the oxidized forms of homocysteine and their derivatives that accumulate in patients when the methionine recycling pathway becomes impaired, as in cardiovascular diseases, neurological/psychiatric disorders and cancer. We have chemically synthesized the homocysteinsulfinic acid (HCSA) and established that it can be converted to homohypotaurine (HHT), a compound not commercially available, via an enzymatic, bio-based route. We will establish the best conditions for the bio-based synthesis and purification of HHT, which will be tested on cardiomyocytes, HUVEC cells and neutrophils.
Furthermore, we will investigate the metabolic role of C-S-containing biomolecules related to taurine. Particular emphasis will be on thiotaurine, a biomolecule releasing hydrogen sulfide (H2S), and on the role of these molecules in controlling inflammation. The specific signaling pathways involved will be dissected and the enzymatic route to its synthesis will be investigated. We aim is to identify the proteins that change their expression level or undergo post-translational modifications, including nitrosylation/nitration, persulfidation. Finally, the effect of H2S will be assessed in pathologies characterized by an increase of oxidative stress, as it occurs in some respiratory diseases such as Chronic Obstructive Pulmonary Disease.

LS1_2, LS6_3, LS9_1

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma