Oleĭnikov V A, Ustinova O A, Mochalov K E, Ermishov M A, Grokhovskiĭ S L, Zhuze A L, Sukhanova A V, Nabiev I R
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia.
Biofizika. 2003 May-Jun;48(3):436-42.
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.
研究了一种杂合分子内酯环的水解动力学，该杂合分子包含抗肿瘤药物喜树碱分子和抗生素纺锤菌素的衍生物，后者对DNA的A-T序列具有高度亲和力和特异性。结果表明，分子内相互作用显著减慢了水解速率，但并未改变杂合分子中喜树碱片段内酯形式和羧酸盐形式浓度的平衡比，该平衡比与pH值相对应。利用分子内相互作用来控制内酯/羧酸盐转变的动力学，使得制备喜树碱家族药物成为可能，这类药物在生理条件下能更长时间地保持生物活性内酯形式，因此作为抗癌剂更有效。
