title: [Kinetics of the lactone-carboxylate transition of hybrid camptothecin-netropsin molecules].
abstract: The kinetics of the hydrolysis of the lactone ring of a hybrid molecule containing the molecules of the antitumor drug camptothecin and a derivative of the antibiotic netropsines, which is highly affine and specific to the DNA A-T sequences was investigated. It was shown that intramolecular interaction significantly slows down the rate of hydrolysis but does not change the equilibrium ratio of concentrations of the lactone and carboxylate forms of the camptothecin fragment of the hybrid molecule, which corresponds to the pH value. The use of intramolecular interaction for controlling the kinetics of the lactone/carboxylate transition makes it possible to create the drugs of the camptothecin family, which preserve the biologically active lactone form under the physiological conditions for a longer time and, therefore, are more effective as anticancer agents.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia. voleinik@nmr.ru
authors.forename: V A
authors.initials: VA
authors.lastname: Oleĭnikov
authors.forename: O A
authors.initials: OA
authors.lastname: Ustinova
authors.forename: K E
authors.initials: KE
authors.lastname: Mochalov
authors.forename: M A
authors.initials: MA
authors.lastname: Ermishov
authors.forename: S L
authors.initials: SL
authors.lastname: Grokhovskiĭ
authors.forename: A L
authors.initials: AL
authors.lastname: Zhuze
authors.forename: A V
authors.initials: AV
authors.lastname: Sukhanova
authors.forename: I R
authors.initials: IR
authors.lastname: Nabiev
mesh_terms: D002166:Camptothecin / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D007783:Lactones / Q000737:chemistry*; D009429:Netropsin / Q000737:chemistry*
chemical_list: D002264:Carboxylic Acids; D007783:Lactones; D009429:Netropsin; D002166:Camptothecin