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Information × Registration Number 0221U101205, 0118U001128 , R & D reports Title Peptides with photo-directed biological activity - inhibitors of intracellular processes involved in the development of cancer diseases. popup.stage_title Head Komarov Igor V., Доктор хімічних наук Registration Date 17-01-2021 Organization Taras Shevchenko National University of Kyiv popup.description2 Object of research: Peptides with photocontrolled biological properties. Purpose: design, synthesis, study of biological activity and development of approaches to the use of such peptides in the treatment of cancer, which contain a diisoletene fragment capable of photoisomerization and are analogs of known peptide inhibitors PIN1 and p53-MDM2 protein-protein interaction - intracellular targets of potential candidates cancer. Research methods: organic synthesis, computer modeling, analysis using physical methods. The synthesis of diarylethene derivatives - amino acid analogues was carried out. Using the synthesized derivatives, photosensitive fragments were introduced into peptide prototypes (intracellular targets) by the method of solid-phase peptide synthesis. Computer-aided design of photosensitive peptides was performed based on the knowledge of target structure published in the literature. New peptides - inhibitors of PIN1 enzyme, including photosensitive ones, which are derivatives of diarylethylene, were synthesized, and their biological activity in relation to the enzyme was studied. The complexes of two photoforms of previously obtained diarylethylene-containing inhibitors with PIN1 were comprehensively studied by the methods of molecular docking and molecular dynamics. It was found that both the structure and dynamic behavior of the complexes differ from each other, which is consistent with the results of experimental measurements. New peptides, inhibitors of p53MDM2 interaction were synthesized. Peptides have been found that show significant activity and photosensitivity. Since most of them do not show activity on cellular bioassays, it is hypothesized that these inhibitors do not penetrate into cells. To test this hypothesis, a conjugate of the best inhibitor with a fragment of a cell-permeable peptide was synthesized and it was found that it not only shows activity and photosensitivity at the target, but also initiates apoptosis of cancer cells.  Product Description popup.authors Harmanchuk Liudmyla Vasylivna popup.nrat_date 2021-01-17 Close