Registration Number
0213U001868,
0110U001413
, R & D reports
Title
The study of structure-function relationships of peptide antibiotics molecules
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Head
Lisnyak Yuriy Volodimirovich,
Registration Date
25-02-2013
Organization
The Mechnikov Research Institute of microbiology and immunology at Kharciv
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Objects of study: polymyxin derivatives. Subject of study: structural characteristics of polymyxin molecules, which should contribute to increase of therapeutic efficacy of antimicrobial compounds of this group; antimicrobial activity of polymyxins. Мethods:molecular modeling, microbiological methods. Results: it was shown that polymyxin molecule is conformationally flexible and is characterized by multiplicity of its possible conformations, basically due to the mobility of side residues of amino acids . Especially important for antimicrobial activity of polymyxins are residues of diaminobutyric acid within the cyclic heptapeptide, whose side chains are cationic and provide the corresponding spatial allocation of positive charges for electrostatic interactions with lipid A phosphates. The probable sites of binding with lipid A were shown to be amino groups of diaminobutyric acids 5 and 9 within polymyxin macrocycle. Based on the comparison of calculated binding constants of complexes of polymyxin with megalin versus literature data of pharmacokinetic studies, it is concluded that the level of polymyxins nephrotoxicity correlates with the peculiarities of their interactions with megalin. There was synthesized succinyl-polymyxin: acylation of polymyxin did not result in increase of its activity against standard strains of gram-negative and gram-positive bacteria. For 33 circulating multi-resistant strains of P. aeruginosa, there was determined sensitivity to polymyxin M. All strains were found to be sensitive to the antibiotic. There was ascertained synergism of polymyxin M and B action with the carbapenem representative against carbapenem-resistant strains of P.aeruginosa.
Product Description
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Баумер В.М.
Давиденко М.Б.
Лісняк Ю.В.
Мартинов А.В.
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2020-04-02
