Sulfur-containing amino acids and their derivatives: from chemical and bio-based synthesis to the investigation of their biological activities
Methionine, an essential amino acid for humans, 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. 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 conditions or only a biomarker remains to be established.
In the present project we will evaluate the biological properties of HCys-derived molecules.
Last year we synthesized HCSA and established that it can be converted into homohypotaurine via a bio-based route. Both compounds are not available commercially. As part of this project, we will find the best conditions for the bio-based synthesis and purification of homohypotaurine. We will test its biological effects both in bacteria and eukaryotic cells. Very little is known on the biological role of homohypotaurine respect to homotaurine, its oxidation product, in widespread pharmaceutical and laboratory use.
Furthermore, we plan to investigate the metabolic role of 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 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. 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.