[Thermodynamic and spectral study of DNA-prospidin complex].
By the methods of heat denaturation and luminescence the interaction between an antitumor drug prospidine and DNA in aqueous solutions at two ionic strengths (0.1 and 0.001 M NaCl) and at various prospidine concentrations was studied. For the first time it has been demonstrated that the interaction occurs at 0.1 M NaCl and therapeutic prospidine concentrations. In the framework of Frank-Kamenetsky's theory of melting of a polymer with stabilizing ligands the size of the binding site and binding constants (K) with the decrease of ionic strength, the lack of alterations in the DNA UV absorption spectrum on complex formation and the data on the competitive binding of ethydium bromide suggest that at the first stage of the reaction an external complex is formed due to electrostatic interactions between quaternary nitrogen atoms of prospidine and DNA phosphate groups. Incubation of the complex at 37 0 C leads to a decrease of the DNA melting temperature and hyperchromic effect. Presumably this is due to the relatively slow formation of chemical bonds between alkylating groups of prospidine and nucleophilic groups of DNA bases, which results in the destabilization and denaturation of DNA. It is concluded that the interaction between prospidine and DNA must be taken into consideration when studying the molecular mechanism of prospidine antitumour activity.
Fedorov
V F
VF
Zozulia
V N
VN
Piatigorskaia
T L
TL
Chernov
V A
VA
Blagoĭ
Iu P
IuP
D000818:Animals; D002645:Chickens; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D004996:Ethidium / Q000378:metabolism; D066298:In Vitro Techniques; D009691:Nucleic Acid Denaturation; D010879:Piperazines / Q000378:metabolism*; D011447:Prospidium / Q000378:metabolism* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
D010879:Piperazines; D011447:Prospidium; D004247:DNA; D004996:Ethidium
Termodinamicheskoe i spektral'noe issledovanie kompleksa DNK s prospidinom.