2-deoxyribose 5-phosphate | 137941-20-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-deoxyribose 5-phosphate
• 英文别名: Deoxyribose 5-phosphate；[(2R,3S,5R)-3,5-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 137941-20-9
• 化学式: C₅H₁₁O₇P
• 分子量: 214.112
• InChiKey: KKZFLSZAWCYPOC-VPENINKCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-deoxyribose 5-phosphate 、 diamino((1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino)platinum(V) chloride nitrate 在 ascorbic acid 作用下， 以 N,N-二甲基甲酰胺-d7 、 水 、 重水 为溶剂， 生成
  参考文献：
  名称：

  Long-Range Distance Constraints in Platinated Nucleotides: Structure Determination of the 5' Orientational Isomer of cis-[Pt(NH3)(4-aminoTEMPO){d(GpG)}]+ from Combined Paramagnetic and Diamagnetic NMR Constraints with Molecular Modeling

  摘要：

  The compound cis-[Pt(NH3)(4-aminoTEMPO)ClI] (7) is a paramagnetic analogue of the anticancer drug cisplatin and of cis-[Pt(NH3)(C6H11NH2)Cl-2] (1), a major metabolite of a recently developed, orally administered derivative. The bifunctional mixed amine complex 7 and a monofunctional triamine complex, trans-[Pt(NH3)(2)(4-aminoTEMPO)Cl]NO3 (8), were synthesized to provide localized unpaired electron spin density for use in NMR spectral studies of their polynucleotide adducts. Compounds 7 and 8 readily coordinate to the N(7) positions of guanosine nucleosides, as revealed by H-1, P-31, and Pt-195 NMR spectroscopy. The NMR spectra were selectively broadened owing to distance-dependent relaxation from the unpaired electron localized on the nitroxyl radical of the 4-aminoTEMPO ligand. Platination of d(GpG) by the mixed amine complex 7 afforded two orientational isomers which differed with respect to the positioning of the 4-aminoTEMPO group toward either the 3' or 5' side of the phosphodiester linkage. The purified orientational isomers were readily distinguished by selective broadening of the H-1 NMR resonances of the 3' and 5' deoxyribose rings. The minimum energy solution structure for the 5' orientational isomer of the platinated dinucleotide cis-[Pt(NH3)(4-aminoTEMPO)(d(GpG)}](+) (13) was determined by NMR methods including combined diamagnetic (J coupling constants) and paramagnetic (electron-H-1, P-31 distances) constraints. Moreover, with the paramagnetic spin probe, we have been able to obtain the first observable NMR distance constraints for determining the configuration of the zeta or alpha torsion angles in any oligonucleotide. Dynamics trajectories (200 ps) for 13 demonstrated that only computations including paramagnetic distance constraints could determine the zeta(-), alpha(-) conformation of the phosphodiester linkage and the conformation of the 4-aminoTEMPO ligand. These NMR data and computational methods demonstrate the utility of long-range paramagnetic distance constraints in elucidating the NMR solution structures of DNA modified by cisplatin analogues.

  DOI：

  10.1021/ja00148a012
• 作为产物：
  描述：

  5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate 在 2'-deoxynucleoside 5′-monophosphate-N-glycosidase 作用下， 生成 5-羟甲基脲嘧啶 、 2-deoxyribose 5-phosphate
  参考文献：
  名称：

  靶向核苷酸挽救因子 DNPH1 使 BRCA 缺陷细胞对 PARP 抑制剂敏感

  摘要：

  BRCA1或BRCA2肿瘤抑制基因的突变使个体易患乳腺癌和卵巢癌。在临床上，这些癌症采用针对聚（ADP-核糖）聚合酶（PARP）的抑制剂进行治疗。我们发现，抑制 DNPH1（一种消除细胞毒性核苷酸 5-羟甲基脱氧尿苷 (hmdU) 单磷酸盐的蛋白质）可增强BRCA缺陷细胞对 PARP 抑制剂 (PARPi) 的敏感性。合成致死性是由 SMUG1 糖基化酶对基因组 hmdU 的作用介导的，导致 PARP 捕获、复制叉塌陷、DNA 断裂形成和细胞凋亡。获得 PARPi 抗性的BRCA1缺陷细胞通过 hmdU 和 DNPH1 抑制处理重新敏感。由于基因组 hmdU 是 PARPi 敏感性的关键决定因素，因此靶向 DNPH1 为BRCA缺陷型癌症对 PARPi 治疗的超敏化提供了一种有前景的策略。

  DOI：

  10.1126/science.abb4542

文献信息

• Human 2′‐Deoxynucleoside 5′‐Phosphate <i>N</i>‐Hydrolase 1: The Catalytic Roles of Tyr24 and Asp80
  作者：Anna E. Carberry、Suneeta Devi、David J. Harrison、Rafael G. da Silva

  DOI：10.1002/cbic.202400047

  日期：2024.4.2

  The human enzyme 2′-deoxynucleoside 5′-phosphate N-hydrolase 1 (HsDNPH1) is a promising target for inhibition towards anticancer drug development. Crystal structures, site-directed mutagenesis, and kinetic analysis, including pH-rate profiles and solvent deuterium isotope effects, help quantify contributions from conserved residues Tyr24 and Asp80 to HsDNPH1-catalysed hydrolysis of 5-hydroxymethyl-2′-deoxyuridine

  人类酶 2'-脱氧核苷 5'-磷酸N-水解酶 1 ( Hs DNPH1) 是抑制抗癌药物开发的一个有前景的靶标。晶体结构、定点诱变和动力学分析（包括 pH 速率曲线和溶剂氘同位素效应）有助于量化保守残基 Tyr24 和 Asp80 对Hs DNPH1 催化的 5-羟甲基-2'-脱氧尿苷 5'- 水解的贡献磷酸盐。这些包括亲核试剂和底物定位以及一般酸催化。
• Ramirez, Fausto; Marecek, James F.; Szamosi, Janos, Phosphorus and Sulfur and the Related Elements, 1982, vol. 13, p. 249 - 258
  作者：Ramirez, Fausto、Marecek, James F.、Szamosi, Janos

  DOI：——

  日期：——
• Long-Range Distance Constraints in Platinated Nucleotides: Structure Determination of the 5' Orientational Isomer of cis-[Pt(NH3)(4-aminoTEMPO){d(GpG)}]+ from Combined Paramagnetic and Diamagnetic NMR Constraints with Molecular Modeling
  作者：Stephen U. Dunham、Stephen J. Lippard

  DOI：10.1021/ja00148a012

  日期：1995.11

  The compound cis-[Pt(NH3)(4-aminoTEMPO)ClI] (7) is a paramagnetic analogue of the anticancer drug cisplatin and of cis-[Pt(NH3)(C6H11NH2)Cl-2] (1), a major metabolite of a recently developed, orally administered derivative. The bifunctional mixed amine complex 7 and a monofunctional triamine complex, trans-[Pt(NH3)(2)(4-aminoTEMPO)Cl]NO3 (8), were synthesized to provide localized unpaired electron spin density for use in NMR spectral studies of their polynucleotide adducts. Compounds 7 and 8 readily coordinate to the N(7) positions of guanosine nucleosides, as revealed by H-1, P-31, and Pt-195 NMR spectroscopy. The NMR spectra were selectively broadened owing to distance-dependent relaxation from the unpaired electron localized on the nitroxyl radical of the 4-aminoTEMPO ligand. Platination of d(GpG) by the mixed amine complex 7 afforded two orientational isomers which differed with respect to the positioning of the 4-aminoTEMPO group toward either the 3' or 5' side of the phosphodiester linkage. The purified orientational isomers were readily distinguished by selective broadening of the H-1 NMR resonances of the 3' and 5' deoxyribose rings. The minimum energy solution structure for the 5' orientational isomer of the platinated dinucleotide cis-[Pt(NH3)(4-aminoTEMPO)(d(GpG)}](+) (13) was determined by NMR methods including combined diamagnetic (J coupling constants) and paramagnetic (electron-H-1, P-31 distances) constraints. Moreover, with the paramagnetic spin probe, we have been able to obtain the first observable NMR distance constraints for determining the configuration of the zeta or alpha torsion angles in any oligonucleotide. Dynamics trajectories (200 ps) for 13 demonstrated that only computations including paramagnetic distance constraints could determine the zeta(-), alpha(-) conformation of the phosphodiester linkage and the conformation of the 4-aminoTEMPO ligand. These NMR data and computational methods demonstrate the utility of long-range paramagnetic distance constraints in elucidating the NMR solution structures of DNA modified by cisplatin analogues.
• Targeting the nucleotide salvage factor DNPH1 sensitizes <i>BRCA</i> -deficient cells to PARP inhibitors
  作者：Kasper Fugger、Ilirjana Bajrami、Mariana Silva Dos Santos、Sarah Jane Young、Simone Kunzelmann、Geoff Kelly、Graeme Hewitt、Harshil Patel、Robert Goldstone、Thomas Carell、Simon J. Boulton、James MacRae、Ian A. Taylor、Stephen C. West

  DOI：10.1126/science.abb4542

  日期：2021.4.9

  poly(ADP-ribose) polymerase (PARP). We show that inhibition of DNPH1, a protein that eliminates cytotoxic nucleotide 5-hydroxymethyl-deoxyuridine (hmdU) monophosphate, potentiates the sensitivity of BRCA-deficient cells to PARP inhibitors (PARPi). Synthetic lethality was mediated by the action of SMUG1 glycosylase on genomic hmdU, leading to PARP trapping, replication fork collapse, DNA break formation

  BRCA1或BRCA2肿瘤抑制基因的突变使个体易患乳腺癌和卵巢癌。在临床上，这些癌症采用针对聚（ADP-核糖）聚合酶（PARP）的抑制剂进行治疗。我们发现，抑制 DNPH1（一种消除细胞毒性核苷酸 5-羟甲基脱氧尿苷 (hmdU) 单磷酸盐的蛋白质）可增强BRCA缺陷细胞对 PARP 抑制剂 (PARPi) 的敏感性。合成致死性是由 SMUG1 糖基化酶对基因组 hmdU 的作用介导的，导致 PARP 捕获、复制叉塌陷、DNA 断裂形成和细胞凋亡。获得 PARPi 抗性的BRCA1缺陷细胞通过 hmdU 和 DNPH1 抑制处理重新敏感。由于基因组 hmdU 是 PARPi 敏感性的关键决定因素，因此靶向 DNPH1 为BRCA缺陷型癌症对 PARPi 治疗的超敏化提供了一种有前景的策略。