Binding of cis- and trans-diamminedichloroplatinum(II) to deoxyribonucleic acid exposes nucleosides as measured immunochemically with anti-nucleoside antibodies.
Binding of cis- and trans-diamminedichloroplatinum(II) to deoxyribonucleic acid exposes nucleosides as measured immunochemically with anti-nucleoside antibodies.
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顺式和反式二氯二氨铂 (II) 与脱氧核糖核酸的结合会暴露核苷(用抗核苷抗体进行免疫化学测量)。
DOI:
10.1021/bi00355a008
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发表时间:
1986
期刊:
影响因子:
2.9
通讯作者:
Stollar,BD
中科院分区:
文献类型:
--
作者:
Sundquist,WI;Lippard,SJ;Stollar,BD
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111 Received June 21, 1985 abstract: We report the use of anti-nucleoside antibodies to probe for local denaturation of calf thymus DNA upon binding of the antitumor drug m-diamminedichloroplatinum (II), m-DDP, and the biologically inactive analogues írazis-diamminedichloroplatinum (II), írans-DDP, and chloro (diethylenetriamine) plat-inum (II) chloride,[Pt (dien) Cl] Cl. These antibodies specifically recognize each of the four DNA nucleosides. They bind well to denatured DNA, but not to native DNA in which the bases are less accessible owing to Watson-Crick duplex structure. At relatively high levels of modification (D/N~0.1), m-DDP causes significant disruption of DNA base pairing as reflected by the increased binding of anti-cytidine, anti-adenosine, and anti-thymidine antibodies. At lower levels of platinum adduct formation, however, all four anti-nucleoside antibodies bind more to DNA modified with trans-DDP. This result indicates that adducts formed by trans-DDP disrupt the DNA structure to a greater extent than those formed by m-DDP at low D/N ratios. Modification of DNA by the monofunctional complex [Pt (dien) Cl] Cl does not affect its recognition by anti-nucleoside antibodies, demonstrating that base pair disruption is a consequence of bifunctional binding. The relative anti-nucleoside antibody recognition of m-DDP-modified DNA is anti-cytosine> anti-adenosine~ anti-thymidine» anti-guanosine, consistent with the major adduct being an intrastrand d (GpG) cross-link. These results reveal that base pair disruption in a naturally occurring DNA modified by either m-DDP or trans-DDP is sufficient to be detected by protein (antibody) binding. The relevance of these findings to current ideas about the molecular mechanism of action of m-DDP is discussed.
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影响因子:
3.7
作者:
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影响因子:
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DOI:
10.1016/0167-4781(83)90106-9
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期刊:
Biochimica et biophysica acta
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