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顺式-[Pt(NH₃)₂(H₂O)₂](NO₃)₂与核糖 脱氧核糖 二鸟苷磷酸的相互作用

Interaction of cis-[Pt(NH3)2(H2O)2](NO3)2 with ribose deoxyribose diguanosine phosphates.

作者信息

Girault J P, Chottard G, Lallemand J Y, Chottard J C

出版信息

Biochemistry. 1982 Mar 16;21(6):1352-6. doi: 10.1021/bi00535a038.

DOI:10.1021/bi00535a038
PMID:6280759
Abstract

The three diguanosine phosphates GpG (4 X 10(-4) M), d(GpG) (10(-5) M), and d(pGpG) (10(-5) M) have been reacted with cis-Pt(NH3)2(H2O)22 (1 Pt/dinucleotide) in water at pH 5.5 and 37 degrees C. In each case a single product is formed. The three complexes have been characterized by proton nuclear magnetic resonance (1H NMR) and circular dichroism (CD) analyses. They are N(7)-N(7) chelates of the metal with an anti-anti configuration of the bases. They present a conformational change upon deprotonation of guanine N(1)H whose pKa is ca. 8.7 (D2O). Their CD spectra, compared to those of the free dinucleotides, exhibit an increase of ellipticity in the 275-nm region, which can be qualitatively related to the characteristic increase reported for platinated DNA and poly(dG) . poly(dC). These results are in favor of the hypothesis of intrastrand cross-linking of adjacent guanines, by the cis-PtII(NH3)2 moiety, after a local denaturation of DNA.

摘要

三种二磷酸鸟苷GpG(4×10⁻⁴ M)、d(GpG)(10⁻⁵ M)和d(pGpG)(10⁻⁵ M)已在pH 5.5和37℃的水中与顺式-Pt(NH₃)₂(H₂O)₂₂(1个铂/二核苷酸)反应。每种情况下都形成了单一产物。这三种配合物已通过质子核磁共振(¹H NMR)和圆二色性(CD)分析进行了表征。它们是金属的N(7)-N(7)螯合物,碱基具有反-反构型。在鸟嘌呤N(1)H去质子化时它们会发生构象变化,其pKa约为8.7(重水)。与游离二核苷酸的CD光谱相比,它们的CD光谱在275 nm区域显示出椭圆率增加,这可以定性地与铂化DNA和聚(dG)·聚(dC)报道的特征性增加相关。这些结果支持这样的假设,即DNA局部变性后,顺式-PtII(NH₃)₂部分会使相邻鸟嘌呤发生链内交联。

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