The requirement for novel platinum antitumor drugs led to the concept of synthesis of novel platinum drugs based on targeting cisplatin to various carrier molecules. We have shown [Loskotova, H., and Brabec, V. (1999) Eur. J. Biochem. 266, 392-402] that attachment of DNA minor-groove-binder distamycin to cisplatin changes several features of DNA-binding mode of the parent platinum drug. Major differences comprise different conformational changes in DNA and a considerably higher interstrand cross-linking efficiency. The studies of the present work have been directed to the analysis of oligodeoxyribonucleotide duplexes containing single, site-specific adducts of platinum-distamycin conjugates. These uniquely modified duplexes were analyzed by Maxam-Gilbert footprinting, phase-sensitive gel electrophoresis bending assay and chemical probes of DNA conformation. The results have indicated that the attachment of distamycin to cisplatin mainly affects the sites involved in the interstrand cross-links so that these adducts are preferentially formed between complementary guanine and cytosine residues. This interstrand cross-link bends the helix axis by approximately 35 degrees toward minor groove, unwinds DNA by approximately 95 degrees and distorts DNA symmetrically around the adduct. In addition, CD spectra of restriction fragments modified by the cisplatin-distamycin conjugates have demonstrated that distamycin moiety in the interstrand cross-links of these compounds interacts with DNA. This interaction facilitates the formation of these adducts. Hence, the structural impact of the specific interstrand cross-link detected in this study deserves attention when biological behavior of cisplatin derivatives targeted by oligopeptide DNA minor-groove-binders is evaluated.

• MeSH
• adukty DNA chemie   MeSH
• brom chemie   MeSH
• cirkulární dichroismus MeSH
• cisplatina chemie   MeSH
• diethylpyrokarbonát chemie   MeSH
• dinukleosidfosfáty chemie   MeSH
• distamyciny chemie   MeSH
• DNA chemie   MeSH
• heteroduplexy nukleové kyseliny chemická syntéza   chemie   MeSH
• jednovláknová DNA chemie   MeSH
• konformace nukleové kyseliny * MeSH
• manganistan draselný chemie   MeSH
• oligodeoxyribonukleotidy chemická syntéza   chemie   MeSH
• pyrimidinové nukleotidy chemická syntéza   chemie   MeSH
• reagencia zkříženě vázaná chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• brom MeSH
• cisplatin-deoxy(guanosine monophosphate guanosine) adduct MeSH Prohlížeč
• cisplatin-DNA adduct MeSH Prohlížeč
• cisplatina MeSH
• deoxyguanylyl-(3'-5')-guanosine MeSH Prohlížeč
• diethylpyrokarbonát MeSH
• dinukleosidfosfáty MeSH
• distamyciny MeSH
• DNA MeSH
• heteroduplexy nukleové kyseliny MeSH
• jednovláknová DNA MeSH
• manganistan draselný MeSH
• oligodeoxyribonukleotidy MeSH
• pyrimidinové nukleotidy MeSH
• reagencia zkříženě vázaná MeSH
• stallimycin MeSH Prohlížeč