The investigation of structure-activity relationship of polyamine-targeted synthetic compounds from different chemical groups.

The investigation of structure-activity relationship of polyamine-targeted synthetic compounds from different chemical groups. Amino Acids. 2019 Sep 13;: Authors: Syatkin SP, Neborak EV, Khlebnikov AI, Komarova MV, Shevkun NA, Kravtsov EG, Blagonravov ML, Agostinelli E Abstract The polyamine (PA) metabolism is involved in cell proliferation and differentiation. Increased cellular PA levels are observed in different types of cancers. Products of PA oxidation induce apoptosis in cancer cells. These observations open a perspective to exploit the enzymes of PA catabolism as a target for anticancer drug design. The substances capable to enhance PA oxidation may become potential anticancer agents. The goal of our study was to explore how the mode of ligand binding with a PA catabolic enzyme is associated with its stimulatory or inhibitory effect upon PA oxidation. Murine N1-acetylpolyamine oxidase (5LFO) crystalline structure was used for molecular docking with ligands of various chemical structures. In vitro experiments were carried out to evaluate the action of the tested compounds upon PA oxidative deamination in a cell-free test system from rat liver. Two amino acid residues (Aps211 and Tyr204) in the structure of 5LFO were found to be significant for binding with the tested compounds. 19 out of 51 screened compounds were activators and 17 were inhibitors of oxidative deamination of PA. Taken together, these results enabled to construc...
Source: Amino Acids - Category: Biochemistry Authors: Tags: Amino Acids Source Type: research