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Information × Registration Number 0220U100090, 0119U103532 , R & D reports Title Structure-functional relationships determining antitumor activity of angucycline antibiotics of landomycin family popup.stage_title Head Panchuk Rostyslav R., Доктор біологічних наук Registration Date 09-01-2020 Organization Institute of Cell Biology popup.description2  Structure-activity relationships of 8 different representatives of the family of landomycin antibiotics differing in the length of the carbohydrate chain and the structure of the aglycone, and the level of induction of oxidative stress under their action in human malignant cells were investigated. It was shown that the highest level of ROS was observed for landomycin A, which contained 6 residues of dideoxysugars, while the lowest was found under the action of landomycinonr (aglycone without oligosaccharide chain). The pattern between the structure of the oligosaccharide chain and the production of ROS was determined, which depends on the presence of the terminal L-rhodinose residue in the landomycin molecule. As a consequence, landomycin B with a 5-membered oligosaccharide chain ending in D-olivose produces three times less ROS than landomycin E, which contains only 3 sugars, but the last one is L-rhodinosis. The lowest ROS-inducible activity was observed for landomycin D, which contained 2 residues of D-olivose, and none – of L-rhodinose. ROS production was practically absent under the action of landomycinone, which did not contain dideoxysugars at all. Therefore, the ability of landomycins to produce hydrogen peroxide directly depends on the presence in their structure of dideoxy sugars, especially L-rhodinose. The ROS-inducible ability of landomycins positively correlated with their cytotoxic activity, where compounds with terminal L-rhodinose residues rather than the longest hydrocarbon chain exhibited the most active action against malignant cells. Elimination of the hydroxyl group at the 11th position of the aglycone of landomycins dramatically (2-fold) increased the production of ROS at early time points (up to 1 h) compared to natural counterparts, but then dynamically dropped further, decreasing by more than 1.5-2-fold. This indicates a complex interplay between aglycone and the oligosaccharide chain of landomycins in realization of their antitumor poten Product Description popup.authors Kashchak Nataliya I. Kozak Yuliia S. Skorokhyd Nadiya R. popup.nrat_date 2020-04-02 Close