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
生物化学系，塔夫茨大学医学院，波士顿，马萨诸塞州02111接收日期：1985年6月21日摘要：我们报告了使用抗核苷抗体来探测小牛胸腺DNA在抗肿瘤药物间二氨二氯铂（II），m-DDP和生物学上无活性的类似物哌嗪二氨二氯铂（II），反式DDP，和氯化（二亚乙基三胺）铂（II）[Pt（dien）Cl] Cl。这些抗体特异性识别四种DNA核苷中的每一种。它们与变性DNA结合良好，但不与天然DNA结合，其中碱基由于沃森-克里克双链体结构而不易接近。在相对较高的修饰水平（D/N~0.1）下，m-DDP导致DNA碱基配对的显著破坏，这反映在抗胞苷、抗腺苷和抗胸苷抗体的结合增加。然而，在较低水平的铂加合物形成下，所有四种抗核苷抗体更多地结合到用trans-DDP修饰的DNA。该结果表明，在低D/N比下，由trans-DDP形成的加合物比由m-DDP形成的加合物更大程度地破坏DNA结构。单功能复合物[Pt（dien）Cl] Cl对DNA的修饰不影响其被抗核苷抗体识别，表明碱基对破坏是双功能结合的结果。m-DDP修饰的DNA的相对抗核苷抗体识别是抗胞嘧啶>抗腺苷~抗胸苷>抗鸟苷，与主要加合物是链内d（GpG）交联一致。这些结果表明，由m-DDP或trans-DDP修饰的天然存在的DNA中的碱基对破坏足以通过蛋白质（抗体）结合来检测。这些发现的相关性，目前的想法m-DDP的作用的分子机制进行了讨论。
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：
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作者：
R. Schreck;Bernard F. Erlanger;O. J. Miller
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DOI：
10.1016/0167-4781(83)90106-9
发表时间：
1983
期刊：
Biochimica et biophysica acta
影响因子：
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作者：
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影响因子：
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作者：
B. V. Hemelryck;E. Guittet;G. Chottard;J. Girault;T. Huynh;J. Lallemand;J. Igolen;J. Chottard
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影响因子：
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作者：
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