SYNTHESIS AND H-1-NMR SPECTROSCOPIC CHARACTERIZATION OF TRANS-[PT(NH3)2(D(APGPGPCPCPT)-N7-A(1),N7-G(3))]
SYNTHESIS AND H-1-NMR SPECTROSCOPIC CHARACTERIZATION OF TRANS-[PT(NH3)2(D(APGPGPCPCPT)-N7-A(1),N7-G(3))]
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DOI：
10.1021/bi00392a011
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发表时间：
1987-09-08
期刊：
影响因子：
2.9
通讯作者：
LIPPARD, SJ
中科院分区：
文献类型：
--
作者：
LEPRE, CA;STROTHKAMP, KG;LIPPARD, SJ
在37℃的水溶液中，反式[Pt(NH3)2Cl2]与[d(ApGpGpCpCpT)]2的钠盐发生反应。C用反相高效液相色谱和紫外光谱进行监测。观察到两个中间体，很可能是单功能加合物，它们随后形成了一个主要的单链产物，以及几个被认为是链间交联产物的聚合物物种。用核磁共振氢谱对单链加合物进行了结构表征。从化学位移对pH的依赖关系、二维同核化学位移相关谱(COSY)以及一维和二维核Overhauser效应(NOESY)实验发现，铂(II)部分与腺嘌呤(1)和鸟嘌呤(3)的N7位配位，其间的鸟嘌呤(2)碱与其邻近残基分离。这种链内1，3加合物诱导主干扭转角的变化，并使腺嘌呤(1)的脱氧核糖环从C2‘’-Endo转变为主要的C3‘-Endo构象。其他脱氧核糖环保持BDNA型构象。反式[Pt(NH3)2{d(ApGpGpCpCpT)-N7-A(1)，N7-G(3)}]的结构不同于以前报道的顺式顺式二磷酸1，2-和1，3-链内寡核苷酸加合物的结构，但与文献报道的两种三核苷酸的反式-顺铂1，3-链内加合物的结构一致。
The reaction of trans-[Pt(NH3)2Cl2] with the sodium salt of [d(ApGpGpCpCpT)]2 in aqueous solution at 37.degree. C was monitored by reversed-phase high-performance liquid chromatography and UV spectroscopy. Two intermediates, most likely monofunctional adducts, were observed, which subsequently formed one predominant single-stranded product, as well as several polymeric species proposed to be interstrand cross-linked products. The single-stranded adduct was structurally characterized by 1H NMR spectroscopy. From the pH dependence of the chemical shifts, two-dimensional homonuclear chemical shift correlation (COSY) spectroscopy, and one- and two-dimensional nuclear Overhauser effect (NOESY) experiments, the platinum(II) moiety was found to be coordinated to the N7 positions of adenine(1) and guanine(3), with the intervening guanine(2) base destacked from its neighboring residues. This intrastrand 1,3 adduct induces changes in the backbone torsion angles and causes the deoxyribose ring of adenine(1) to switch from a C2''-endo to a predominantly C3''-endo conformation. The other deoxyribose rings retain B DNA type conformations. The structure of trans-[Pt(NH3)2{d(ApGpGpCpCpT)-N7-A(1),N7-G(3)}] differs from those previously reported for cis-DDP 1,2- and 1,3-intrastrand oligonucleotide adducts but is consistent with the structures of trans-DDP 1,3-intrastrand adducts of two previoulsy reported trinucleotides.