2'-Desoxyguanylyl-(3'-5')-2'-desoxyguanosin | 15180-30-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （3'->5'）-二核苷酸和类似物
• 英文名称: 2'-Desoxyguanylyl-(3'-5')-2'-desoxyguanosin
• 英文别名: 2'-Deoxyguanylyl-(3'-5')-2'-deoxyguanosine；[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] [(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methyl hydrogen phosphate
• CAS: 15180-30-0
• 化学式: C₂₀H₂₅N₁₀O₁₀P
• 分子量: 596.453
• InChiKey: KGXGIPRRDQWVET-WGWHJZDNSA-N

物化性质

• 密度：
  2.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  285
• 氢给体数：
  7
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  [SP-4-2-(1R-反式)]-(1,2-环己烷二胺-N,N')二氯化物铂(II) 、 2'-Desoxyguanylyl-(3'-5')-2'-desoxyguanosin 以 not given 为溶剂， 生成
  参考文献：
  名称：

  Differences in binding of (1,2-cyclohexanediamine)platinum(II) isomers with d(GpG)

  摘要：

  DOI：

  10.1021/ic00221a001
• 作为产物：
  描述：

  N²-isobutyryl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyguanosine 在 二异丙基铵盐四氮唑 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 2'-Desoxyguanylyl-(3'-5')-2'-desoxyguanosin
  参考文献：
  名称：

  使用2-二苯基甲基甲硅烷基乙基（DPSE）作为磷保护基的亚磷酰胺方法合成寡核苷酸

  摘要：

  2-二苯基甲基甲硅烷基乙基（DPSE）是通过亚磷酰胺方法合成寡脱氧核糖核苷酸中核苷酸间键的新保护基。该基团在酸性条件下稳定，可以在温和的β片段化条件下使用氢氧化铵水溶液除去。

  DOI：

  10.1016/s0040-4020(01)85503-4

文献信息

• A Rare Example of Three Abundant Conformers in One Retro Model of the Cisplatin−DNA d(GpG) Intrastrand Cross Link. Unambiguous Evidence That Guanine O6 to Carrier Amine Ligand Hydrogen Bonding Is Not Important. Possible Effect of the Lippard Base Pair Step Adjacent to the Lesion on Carrier Ligand Hydrogen Bonding in DNA Adducts
  作者：Sharon T. Sullivan、Antonella Ciccarese、Francesco P. Fanizzi、Luigi G. Marzilli

  DOI：10.1021/ja010483m

  日期：2001.9.1

  hindering dynamic motion in Me(2)ppzPt(d(GpG)) and Me(2)ppzPt(GpG) retro models. Dynamic processes are decreased enough in Me(2)ppzPt(d(GpG)) to permit HPLC separation of three abundant forms. After HPLC separation, the three re-equilibrate, proving that the three forms must be conformers and that Me(2)ppz has little influence on conformer distribution. This marks the first reported characterization of three

  鸟嘌呤O6与载体配体的氢键结合是许多假设的主要特征，这些假设先进地解释了顺式抗癌药cis-PtA（2）X（2）（A（2）=二胺或两种胺）的抗癌活性。早期的结构证据表明，顺式-Pt（NH（3））（2）（d（GpG））（关键的顺铂-DNA加合物的交联模型）和其他顺式-PtA（2）（d（GpG）） ）加合物专门或主要作为具有头对头（HH）碱基的HH1构象体存在。这些加合物中d（GpG）的动态运动太快，无法确定构象和H键的特征。因此，我们使用具有A（2）配体的复古模型来减慢运动。在这里，我们使用Me（2）ppz（N，N'-二甲基哌嗪），它缺少NH基团。Me（2）ppz的独特之处在于直接在配位平面中具有sp（3）N-甲基，允许多个构象元共存，但阻碍了Me（2）ppzPt（d（GpG））和Me（2）ppzPt（GpG）复古模型中的动态运动。Me（2）ppzPt（d（GpG））中的动态过程降低得足够少，
• Isomer formation in the binding of [PtCl2(cis-cyclohexane-1,3-diamine)] to oligonucleotides and the X-ray crystal structure of [PtCl2(cis-cyclohexane-1,3-diamine)]·dimethylformamide†
  作者：S. Tsuey Cham、Connie I. Diakos、Leanne T. Ellis、Ronald R. Fenton、Vivienne P. Munk、Barbara A. Messerle、Trevor W. Hambley

  DOI：10.1039/b104502b

  日期：——

  The crystal structure of [PtCl2(cis-1,3-chxn)] (cis-1,3-chxn = (cis-cyclohexane-1,3-diamine)) as the dimethyformamide solvate is reported. When [PtCl2(cis-1,3-chxn)] binds to d(GpG), two isomers are formed that are readily separated by HPLC. Both the HPLC and GFAAS studies of the products show that the isomers form in a 1 ∶ 1 ratio. Competition experiments involving d(GpG) and the aquated and nonaquated forms of [PtCl2(cis-1,3-chxn)] and [PtCl2(NH3)2] showed that the slower binding of the former complex was due to slower aquation and not steric bulk. 1D and 2D NMR studies of the [Ptd(GpG)(cis-1,3-chxn)] isomers showed that both the dinucleotide and the diamine were highly fluxional, even at low temperatures, and this prevented formation of strong cross peaks in the NOESY and ROESY spectra and hence identification of the isomers. [PtCl2(cis-1,3-chxn)] was reacted with a 52-mer oligonucleotide having six GpG binding sites and the products were enzymatically digested and separated by HPLC. The two [Ptd(GpG)(cis-1,3-chxn)] stereoisomers were the only significant platinated products, again forming in a 1 ∶ 1 ratio although it had been anticipated that stereoselectivity would be observed in the reaction with the 52-mer because of the potential for steric interactions with the cis-1,3-chxn ligand. Molecular modelling revealed that the observed lack of stereoselectivity was due to the ability of the cis-1,3-chxn ligand to adopt a continuum of conformations that allow it to avoid severe steric clashes with the DNA.

  报告了[PtCl2(cis-1,3-chxn)]（cis-1,3-chxn = (cis-cyclohexane-1,3-diamine)）二甲基甲酰胺溶液的晶体结构。当[PtCl2(cis-1,3-chxn)]与 d(GpG)结合时，会形成两种异构体，并很容易通过 HPLC 分离出来。对产物进行的 HPLC 和 GFAAS 研究表明，这两种异构体的形成比例为 1 ∶ 1。涉及 d(GpG)和[PtCl2(cis-1,3-chxn)]及[PtCl2(NH3)2]的含水和非含水形式的竞争实验表明，前一种复合物的结合速度较慢是由于含水速度较慢，而不是由于立体体积。对[Ptd(GpG)(cis-1,3-chxn)]异构体进行的一维和二维核磁共振研究表明，即使在低温下，二核苷酸和二胺都具有很强的通性，这阻碍了在 NOESY 和 ROESY 光谱中形成强交叉峰，从而无法识别异构体。[PtCl2(顺式-1,3-chxn)]与具有六个 GpG 结合位点的 52 聚合寡核苷酸反应，产物经酶消化后通过高效液相色谱分离。两种[Ptd(GpG)(cis-1,3-chxn)]立体异构体是唯一重要的板化产物，同样以 1 ∶ 1 的比例形成，尽管由于与顺式-1,3-chxn 配体可能发生立体相互作用，预计在与 52-mer 反应中会观察到立体选择性。分子模型显示，之所以观察到缺乏立体选择性，是因为顺式-1,3-chxn 配体能够采用连续的构象，从而避免与 DNA 发生严重的立体冲突。
• Single-Stranded Oligonucleotide Adducts Formed by Pt Complexes Favoring Left-Handed Base Canting: Steric Effect of Flanking Residues and Relevance to DNA Adducts Formed by Pt Anticancer Drugs
  作者：Jamil S. Saad、Patricia A. Marzilli、Francesco P. Intini、Giovanni Natile、Luigi G. Marzilli

  DOI：10.1021/ic2011716

  日期：2011.9.5

  information relevant to the assessment of such duplex effects, we examine (S,R,R,S)-BipPt(oligo) adducts (Bip = 2,2′-bipiperidine with S,R,R,S chiral centers at the N, C, C, and N chelate ring atoms, respectively; oligo = d(G*pG*) with 3′- and/or 5′-substituents). The moderately bulky (S,R,R,S)-Bip ligand favors L canting and slows rotation about the Pt–G* bonds, and the (S,R,R,S)-BipPt(oligo) models

  铂类抗癌药与DNA的结合会在交联（G * G *）和相邻的XG *碱基对（bp）步骤（G * = N7镀金的G）中产生较大的变形。负责抗癌活性的这些畸变取决于双链体（例如碱基配对）和交联部分的特征（例如G *碱基的位置和倾斜）。双工结构可在头尾（HT）方向上稳定头对头（HH），在G *基的左手（L）倾斜方向上使右手（R）稳定。为了提供与评估此类双链体效应有关的基本化学信息，我们研究了（S，R，R，S）-Bip Pt（寡核苷酸）加合物（Bip = 2,2'-bipiperidine与S，R，R，S手性中心分别在N，C，C和N个螯合环原子上; 寡聚＝具有3'-和/或5'-取代基的d（G * pG *）。中等体积的（S，R，R，S）-Bip配体有利于L倾斜并减缓围绕Pt–G *键的旋转，而（S，R，R，S）-Bip Pt（oligo）模型提供了更有用的功能数据比从活性Pt药物得到的动态模型要好。（S，R，R，S）-Bip
• NMR Studies of Models Having the Pt(d(GpG)) 17-Membered Macrocyclic Ring Formed in DNA by Platinum Anticancer Drugs: Pt Complexes with Bulky Chiral Diamine Ligands
  作者：Jamil S. Saad、Michele Benedetti、Giovanni Natile、Luigi G. Marzilli

  DOI：10.1021/ic200259s

  日期：2011.5.16

  macrocyclic ring formed by cisplatin anticancer drug binding to DNA alters the structure of the G*G* base pair steps, canting one base, and increases dynamic motion, complicating solution structural studies. However, the ring appears to favor the HH1 conformation (HH1 denotes head-to-head guanine bases, 1 denotes the normal direction of backbone propagation). Compared to cisplatin, analogues with NH groups

  由顺铂抗癌药与DNA结合形成的高度扭曲的Pt（d（G * pG *））（G * = N7镀金的G）17元大环改变了G * G *碱基对步骤的结构，导致一个基础，并增加动态运动，使解决方案的结构研究复杂化。但是，该环似乎有利于HH1构象（HH1表示头对头鸟嘌呤碱基，1表示骨架传播的法线方向）。与顺铂相比，在载体配体中具有NH基团的类似物被庞大的N-烷基取代，具有更高的毒性和活性，并且形成的动态加合物较少。为了检查空间起源的生物学效应的分子起源，我们评估了Me 4 DAB Pt（d（G * pG *））模型；Me 4 DAB的体积和手性（在螯合环碳原子上具有S，S或R，R构型的N，N，N ′，N′-四甲基-2,3-二氨基丁烷）阻碍了动态运动，并增强了NMR方法用于鉴定和表征构象异构体的效用。不同于以往对带有这种庞大的载体配体的加合物的研究，在其中没有发现HH构象异构体，Me 4 DAB Pt（d（G
• Synthesis of Oligo(Deoxyribonucleoside Phosphorodithioate)s by the Dithiaphospholane Approach
  作者：Andrzej Okruszek、Agnieszka Sierzcha-la、Karen L. Fearon、Wojciech J. Stec

  DOI：10.1021/jo00126a060

  日期：1995.10

  A novel method of synthesis of oligo(deoxyribonucleoside phosphorodithioate)s (S-2-ODNs), based on the ring-opening condensation of nucleoside 3'-0-(2-thiono-1,3,2-dithiaphospholane)s with 5'-O-deprotected nucleosi(ti)des in the presence of a strong organic base such as DBU, is presented. The process has been adapted to the requirements of automated solid-phase oligonucleotide synthesis with a relatively short condensation step (5 min) and reasonable step-yield(>95%). N-Methylpyrrolidin-2-ylidenyl (Pya) was found to be the group of choice for the protection of reactive aminofunctions of nucleobases in nucleotide substrates. Sarcosine-containing linker (LCA CPG SAR) was employed due to its known resistance to cleavage by DBU. Several medium-size S-2-ODNs were prepared by this approach. Their identity and purity was confirmed by means of P-31 NMR, gel electrophoresis, and mass spectrometry. It has been demonstrated that, contrary to a recent report, S-2-ODNs are not degraded by DNaseI.