INTERACTION OF CIS-[PT(NH3)2(H2O)2](NO3)2 WITH RIBOSE AND DEOXYRIBOSE DIGUANOSINE PHOSPHATES
INTERACTION OF CIS-[PT(NH3)2(H2O)2](NO3)2 WITH RIBOSE AND DEOXYRIBOSE DIGUANOSINE PHOSPHATES
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DOI：
10.1021/bi00535a038
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发表时间：
1982-01-01
期刊：
影响因子：
2.9
通讯作者：
CHOTTARD, JC
中科院分区：
文献类型：
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作者：
GIRAULT, JP;CHOTTARD, G;CHOTTARD, JC
GpG [核糖二鸟苷一磷酸; 4 ×10-4 M]、d（GpG）[脱氧核糖二鸟苷一磷酸; 10-5 M]和d（pGpG）[脱氧核糖二鸟苷二磷酸; 10-5 M]与抗肿瘤剂顺式-[Pt（NH3）2（H2O）2]（NO3）2 [顺式-二氨二水合二硝酸铂]（Pt/二核苷酸）在水中于pH5.5和37 ℃反应。C.在每种情况下，形成单一产品。通过核磁共振氢谱和圆二色性谱对3种配合物进行了表征。它们是N（7）-N（7）金属螯合物，具有反-反构型的碱基。它们在PKa为λ的鸟嘌呤N（1）H的去质子化时呈现构象变化。8.7（D2O）。与游离二核苷酸的CD光谱相比，它们的CD光谱在275 nm区域表现出椭圆率的增加，这可以定性地与plantinated DNA和poly（dG）. cntdot报告的特征性增加相关。聚（dC）。这些结果是在相邻的鸟嘌呤链内交联的假设，由顺式-PtII（NH 3）2部分，DNA的局部变性后，有利。
GpG [ribose diguanosine monophosphate; 4 .times. 10-4 M], d(GpG) [deoxyribose diguanosine monophosphate; 10-5 M] and d(pGpG) [deoxyribose diguanosine diphosphate; 10-5 M] were reacted with the antitumor agent cis-[Pt(NH3)2(H2O)2](NO3)2 [cis-diammine diaquoplatinum dinitrate] (Pt/dinucleotide) in water at pH 5.5 and 37.degree. C. In each case a single product is formed. The 3 complexes were characterized by proton NMR (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 on deprotonation of guanine N(1)H whose pKa is .apprx. 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 plantinated DNA and poly(dG) .cntdot. 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.