Sulfur-containing amino acids and their derivatives: from chemical and bio-based synthesis to the investigation of their biological activities
|Carlotta Zamparelli||Componenti il gruppo di ricerca|
|Elisabetta Capuozzo||Componenti il gruppo di ricerca|
|FABIO GIOVANNERCOLE||dottorando XXXI ciclo||Dipartimento di Scienze e Biotecnologie Medic-Chirurgiche||Altro personale Sapienza o esterni|
|EUGENIA PENNACCHIETTI||borsista post-doc||Istituto Pasteur||Altro personale Sapienza o esterni|
|ALESSANDRO CHINAZZI||tecnico||Dipartimento di Bcienze Biochimiche||Altro personale Sapienza o esterni|
In all organisms methionine is an important amino acid in proteins as well as the key component of S-adenosyl methionine (SAM), the main donor of methyl groups in the biosynthesis of biomolecules like choline, creatine, and adrenaline, as well as in DNA methylation. While bacteria possess biosynthetic pathways for methionine, this amino acid is essential for humans. Following SAM demethylation, homocysteine (HCys) is formed. HCys accumulates when its recycling pathways become impaired, leading to hyperhomocysteinemia, that is typical in cardiovascular diseases, neurological/psychiatric disorders and cancer. Whether excessive HCys is causing the pathological condition or is only a biomarker of a metabolic aberration still remains to be established.
In the present project we will evaluate the biological properties of HCys-derived molecules.
First of all we propose a bio-based route for the synthesis of homohypotaurine, the decarboxylation product of homocystein sulfinic acid (HCSA). Both compounds are not available from commercial suppliers. Thus a chemical synthesis and an enzyme-mediated synthesis will be employed to synthesize HCSA and homohypotaurine, respectively. The biological effects of homohypotaurine, both in bacteria and in mammals, are less known than those of homotaurine, its oxidation product,in widespread pharmaceutical and laboratory use. With this project we therefore aim to fill this gap of knowledge.
Furthermore, we plan to investigate the metabolic role of biomolecules related to taurine. Particular emphasis will be devoted to thiotaurine, a biomolecule releasing hydrogen sulfide (H2S), and to the role of these molecules in controlling inflammation. The specific signaling pathways involved will be dissected and proteomic profiling of human neutrophils carried out. The aim of this study is to identify the proteins that change their expression level or undergo post-translational modifications, including nitrosylation/nitration, persulfidation.