Phosphine modification of proline-glycine-proline tripeptide and study of its neuroprotective properties

Treatment of neurodegenerative diseases, such as Parkinson’s disease, Huntington’s chorea, Alzheimer’s disease, is one of the priority directions in modern medicine. Thus, search and production of new physiologically active substances for the treatment of neurodegenerative disorders is one of the most important tasks for organic chemistry. The approach based on the replacement of a peptide bond in a peptide molecule with a structural isostere, non-hydrolyzable methylene phosphoryl fragment makes it possible to increase the metabolic stability of peptide molecules to the destructive action of peptidases. This work is devoted to the approbation of a new synthetic approach to the production of physiologically active substances in a series of peptide-type compounds with activity by replacing the peptide bond with isosteric methylene-phosphoryl fragment with the preservation of the original amino acid sequence. A phosphine analog of the known physiologically active tripeptide proline-glycine-proline was obtained, cytotoxicity and neuroprotective properties of the initial tripeptide and its phosphine analog were studied. Preliminary biological tests have shown that the obtained phosphine analog of the proline-glycine-proline tripeptide is involved in modulating the formation of sediments in the cellular system of proteinopathy, which may indicate their potential antiaggregatory properties. •It has been a successful synthesis of phosphine analog of tripeptide proline-glycine-proline.•When replacing the peptide bond in the peptide molecule methylene-phosphoryl fragment is increased toxicity.•Preliminary biological tests showed that the obtained phosphine analog of the proline-glycine-proline tripeptide has antiaggregatory properties.