[Interaction of topotecan, DNA topoisomerase I inhibitor, with double-stranded polydeoxyribonucleotides. III. Binding at the minor groove].
Interaction of topotecan (TPT) with calf thymus DNA, coliphage T4 DNA, and poly(dG-dC). poly(dG-dC) was studied by optical (linear flow dichroism, UV-vis spectroscopy) and quantum chemical methods. The linear dichroism (LD) signal of TPT bound to DNA was shown to have positive sign in the range 260-295 nm. This means that the plane of quinoline fragment (rings A and B) of TPT molecule form an angle lower 54 degrees with the long axis of DNA, and hence TPT molecule can not intercalate between DNA base pairs. TPT was established to bind to calf thymus DNA as readily as to coliphage T4 DNA whose all cytosines in the major groove were glycosylated at the 5th position. Consequently, the DNA major groove does not participate in TPT binding. TPT molecule was shown to compete with distamycin for binding sites in the minor groove of DNA and poly(dG-dC). poly(dG-dC). Thus, it was demonstrated for the first time that TPT binds to DNA at its minor groove.
Strel'tsov
S A
SA
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia. strelcov@imb.ac.ru
Mikheĭkin
A L
AL
Grokhovskiĭ
S L
SL
Oleĭnikov
V A
VA
Zhuze
A L
AL
D020029:Base Pairing; D001665:Binding Sites; D001667:Binding, Competitive; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004214:Distamycins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D055095:Optics and Photonics; D011068:Poly G; D011089:Polydeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000737:chemistry / Q000378:metabolism*
D004214:Distamycins; D004791:Enzyme Inhibitors; D011089:Polydeoxyribonucleotides; D059004:Topoisomerase I Inhibitors; D011068:Poly G; C026628:poly(dG); D019772:Topotecan; C030000:stallimycin; D004247:DNA
Vzaimodeĭstvie topotekana--ingibitora DNK-topoizomerazy I--s dvunitevymi polidezoksiribonukleotidami. III. Mesto sviazyvaniia--uzkaia borozdka.