Phosphinic modification of GPE tripeptide and simulation of its properties

The search and production of new physiologically active substances to treat neurodegenerative disorders is essential for organic chemistry. The approach based on replacing a peptide bond in a peptide molecule with a structural isostere, non-hydrolyzable methylene phosphoryl fragment makes it possible to increase the metabolic stability peptide molecules to the destructive action of peptidases. In this work, we modified the glycine-proline-glutamate (GPE) tripeptide, which has neuroprotective properties, by replacing the peptide bond C(O)NH in the peptide molecule with a structural isostere non-hydrolyzable methylene phosphoryl fragment P(O)CH2. Using the PASS and GUSAR programs, a prediction and relative comparison of the biological activity and toxicity of the parent tripeptide and its phosphine analog were carried out.