2'-O-[(N-phthalimido)propa-3-yl]guanosine | 160526-97-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2'-O-[(N-phthalimido)propa-3-yl]guanosine
• 英文别名: 2'-o-[(N-phthalimido)prop-3-yl]guanosin；2'-O-(3-N-phthalimidopropyl)guanosine；2-[3-[(2R,3R,4R,5R)-2-(2-amino-6-oxo-1H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxypropyl]isoindole-1,3-dione
• CAS: 160526-97-6
• 化学式: C₂₁H₂₂N₆O₇
• 分子量: 470.442
• InChiKey: ALONGTFKUKEDMF-FNSSNTJLSA-N

物化性质

• 密度：
  1.81±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2'-O-[(N-phthalimido)propa-3-yl]guanosine 在 三乙胺 、 肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 32.0h， 生成 N-[3-[(2R,3R,4R,5R)-2-(2-amino-6-oxo-1H-purin-9-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl]oxypropyl]-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  2‘-O-Aminopropyl Ribonucleotides:  A Zwitterionic Modification That Enhances the Exonuclease Resistance and Biological Activity of Antisense Oligonucleotides

  摘要：

  Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine (APC), 2'-O-(aminopropyl)guanosine (APG), and 2'-O-(aminopropyl)uridine (APU) have been prepared in high yield from the ribonucleoside, protected, and incorporated into an oligonucleotide using conventional phosphoramidite chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the sugar pucker of the nucleoside but does not form a tight ion pair with the proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using NMR. As predicted from the modeling results, the sugar pucker of the APU moiety is shifted toward a C3'-endo geometry. In addition, the primary amine rotates freely and is not bound electrostatically to any phosphate group, as evidenced by the different sign of the NOE between sugar proton resonances and the signals from the propylamine chain. Incorporation of aminopropyl nucleoside residues into point-substituted and fully modified oligomers does not decrease the affinity for complementary RNA compared to 2'-O-alkyl substituents of the same length. However, two APU residues placed at the 3'-terminus of an oligomer gives a 100-fold increase in resistance to exonuclease degradation, which is greater than observed for phosphorothioate oligomers. These structural and biophysical characteristics make the 2'-O-aminopropyl group a leading choice for incorporation into antisense therapeutics. A 20-mer phosphorothioate oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted against C-raf mRNA has been transfected into cells via electroporation. This oligonucleotide has 5-10-fold greater activity than the control phosphorothioate for reducing the abundance of C-raf mRNA and protein.

  DOI：

  10.1021/jm950937o
• 作为产物：
  描述：

  2-氨基腺嘌呤核苷 在 sodium hydride 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 121.0h， 生成 2'-O-[(N-phthalimido)propa-3-yl]guanosine
  参考文献：
  名称：

  假结的形成为 Twister 核酶裂解反应坐标奠定了基础

  摘要：

  twister RNA 是最近发现的一种溶核核酶，存在于细菌和真核生物中。虽然其生物学作用尚不清楚，但晶体结构分析和生化方法已经揭示了其催化机制的关键特征。在这里，我们着手探索沿裂解反应坐标扭曲 RNA 折叠的动态方面。为此，我们采用了批量和单分子荧光共振能量转移 (FRET) 方法来研究一组 Twister RNA，这些 RNA 的标签策略性地定位在通信片段上。数据表明，中央假结 (T1) 的折叠是促进裂解的最关键的结构决定因素，在生理 Mg2+ 浓度下表现出可逆的打开和关闭动力学。使用由 Mg2+ 注射引发的前稳态三色 smFRET 实验证实了非耦合折叠，其中 T1 形成先于茎 P1 闭合的结构化。这一发现表明，Twister RNA 的折叠路径需要在 T1 闭合之前正确定位底物，以便包围 U5-A6 切割位点以实现其切割能力构象。我们还发现，尽管不存在系统发育上保守的茎 P1，但切割的

  DOI：

  10.1021/jacs.7b01549

文献信息

• Oligonucleotides containing 2'-0-modified purines
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20040048826A1

  公开（公告）日：2004-03-11

  Novel 2′-O-alkyl guanosine compounds are provided. In accordance with preferred embodiments compounds having the structure: 1 wherein X is R 1 —(R 2 ) n ; R 1 is C 3 -C 20 alkyl, C 4 -C 20 alkenyl or C 2 -C 20 alkynyl; R 2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6, are provided.

  本发明提供了新型的2'-O-烷基鸟苷化合物。根据优选实施例，所提供的化合物具有以下结构：1其中X为R1-(R2)n；R1为C3-C20烷基、C4-C20烯基或C2-C20炔基；R2为卤素、羟基、硫醇、酮、羧基、硝基、亚硝基、腈、三氟甲基、三氟甲氧基、O-烷基、S-烷基、NH-烷基、N-二烷基、O-芳基、S-芳基、NH-芳基、O-芳基烷基、S-芳基烷基、NH-芳基烷基、氨基、N-邻苯二甲酰亚胺基、咪唑基、叠氮基、肼基、羟胺基、异氰酸酯基、亚砜基、磺酰基、硫醚基、二硫化物基、硅烷基、芳基、杂环、碳环、插入剂、报告分子、共轭物、多胺、多酰胺、多烷基氧基、多醚、增强寡核苷酸药效学性质的基团或增强寡核苷酸药代动力学性质的基团；n为0到约6的整数。
• US5506351A
  申请人：——

  公开号：US5506351A

  公开（公告）日：1996-04-09
• US7101993B1
  申请人：——

  公开号：US7101993B1

  公开（公告）日：2006-09-05
• 2‘-<i>O</i>-Aminopropyl Ribonucleotides:  A Zwitterionic Modification That Enhances the Exonuclease Resistance and Biological Activity of Antisense Oligonucleotides
  作者：Richard H. Griffey、Brett P. Monia、Lendall L. Cummins、Susan Freier、Michael J. Greig、Charles J. Guinosso、Elena Lesnik、Sherilynn M. Manalili、Venkatraman Mohan、Steven Owens、Bruce R. Ross、Henri Sasmor、Ed Wancewicz、Kurt Weiler、Patrick D. Wheeler、P. Dan Cook

  DOI：10.1021/jm950937o

  日期：1996.1.1

  Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine (APC), 2'-O-(aminopropyl)guanosine (APG), and 2'-O-(aminopropyl)uridine (APU) have been prepared in high yield from the ribonucleoside, protected, and incorporated into an oligonucleotide using conventional phosphoramidite chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the sugar pucker of the nucleoside but does not form a tight ion pair with the proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using NMR. As predicted from the modeling results, the sugar pucker of the APU moiety is shifted toward a C3'-endo geometry. In addition, the primary amine rotates freely and is not bound electrostatically to any phosphate group, as evidenced by the different sign of the NOE between sugar proton resonances and the signals from the propylamine chain. Incorporation of aminopropyl nucleoside residues into point-substituted and fully modified oligomers does not decrease the affinity for complementary RNA compared to 2'-O-alkyl substituents of the same length. However, two APU residues placed at the 3'-terminus of an oligomer gives a 100-fold increase in resistance to exonuclease degradation, which is greater than observed for phosphorothioate oligomers. These structural and biophysical characteristics make the 2'-O-aminopropyl group a leading choice for incorporation into antisense therapeutics. A 20-mer phosphorothioate oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted against C-raf mRNA has been transfected into cells via electroporation. This oligonucleotide has 5-10-fold greater activity than the control phosphorothioate for reducing the abundance of C-raf mRNA and protein.
• Pseudoknot Formation Seeds the Twister Ribozyme Cleavage Reaction Coordinate
  作者：Nikola Vušurović、Roger B. Altman、Daniel S. Terry、Ronald Micura、Scott C. Blanchard

  DOI：10.1021/jacs.7b01549

  日期：2017.6.21

  RNA folding along the cleavage reaction coordinate. To do so, we have employed both bulk and single-molecule fluorescence resonance energy transfer (FRET) methods to investigate a set of twister RNAs with labels strategically positioned at communicating segments. The data reveal that folding of the central pseudoknot (T1), the most crucial structural determinant to promote cleavage, exhibits reversible

  twister RNA 是最近发现的一种溶核核酶，存在于细菌和真核生物中。虽然其生物学作用尚不清楚，但晶体结构分析和生化方法已经揭示了其催化机制的关键特征。在这里，我们着手探索沿裂解反应坐标扭曲 RNA 折叠的动态方面。为此，我们采用了批量和单分子荧光共振能量转移 (FRET) 方法来研究一组 Twister RNA，这些 RNA 的标签策略性地定位在通信片段上。数据表明，中央假结 (T1) 的折叠是促进裂解的最关键的结构决定因素，在生理 Mg2+ 浓度下表现出可逆的打开和关闭动力学。使用由 Mg2+ 注射引发的前稳态三色 smFRET 实验证实了非耦合折叠，其中 T1 形成先于茎 P1 闭合的结构化。这一发现表明，Twister RNA 的折叠路径需要在 T1 闭合之前正确定位底物，以便包围 U5-A6 切割位点以实现其切割能力构象。我们还发现，尽管不存在系统发育上保守的茎 P1，但切割的