Interaction of the antitumor antibiotic mitomycin C with Z-DNA.
Interaction of the antitumor antibiotic mitomycin C with Z-DNA.
复制标题
抗肿瘤抗生素丝裂霉素 C 与 Z-DNA 的相互作用。
DOI:
10.1080/07391102.1988.10506500
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发表时间:
1988
影响因子:
4.4
通讯作者:
Tomasz,M
中科院分区:
文献类型:
--
作者:
Chawla,AK;Tomasz,M
Mitomycin C (MC), an antitumor antibiotic, alkylated Z-DNAs such as poly(dG-dC)/CO(NH3)3+6, poly(dG-m5dC)/Mg2+and brominated poly(dG-dC) upon reductive activation. Computer-generated energy-minimized molecular models indicated that monofunctional alkylation of Z-DNA at the N2-position of guanine by MC did not distort Z-DNA geometry, but bifunctional alkylation, leading to interstrand crosslinks between two N2-positions of guanine was sterically unfavorable. The above three Z-DNA's were exposed both to mono-functionally and bifunctionally activated MC in separate experiments and the resulting covalent MC-polynucleotide complexes were examined for conformation and for covalent MC-adducts, by circular dichroism (CD) spectroscopy and HPLC analysis of nuclease digests, respectively. Monofunctionally activated MC alkylated all three polynucleotides in their Z-forms, resulting in the same monofunctional N2-guanine adduct as that known to be formed with B-DNA Upon bifunctional activation of MC, poly(dG-dC)/Co(NH3)63+reverted to the B-form and bifunctional (cross-link) adducts were detected, identical again with those formed with B-DNA Poly(dG-m5dC), however, remained in the Z-form after the alkylation and only a monofunctional adduct could be detected. It was concluded that Z-DNA is subject to monofunctional alkylation by MC but cannot be cross-linked. The latter process occurs only when the Z-DNAis labile enough [as is in the case of poly(dG-dC)] to have some B-form in equilibrium at the site of the first formed monolinked adduct; the cross-linking then occurs at such local B-sites, pulling the overall B⇌Z equilibrium irreversibly to the left. These results are in accord with the predictions from the above modeling. The irreversible “lock” by the MC cross-link on B-DNA may be exploited for probing Z-DNA intermediacy in various DNA functions.
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DOI:
10.1073/pnas.85.1.36
发表时间:
1988
影响因子:
11.1
作者:
Fishel,RA;Detmer,K;Rich,A
通讯作者:
Rich,A
影响因子:
56.9
作者:
A. Nordheim;W. Hao;G. Wogan;A. Rich
通讯作者:
A. Rich
影响因子:
2.9
作者:
Walker,GT;Stone,MP;Krugh,TR
通讯作者:
Krugh,TR
DOI:
--
发表时间:
1989
期刊:
影响因子:
--
作者:
A. Walter
通讯作者:
A. Walter
影响因子:
4.7
作者:
I. Zegar;P. Lycksell;A. Gräslund;M. Eriksson;B. Nordén;B. Jernström
通讯作者:
B. Jernström