3-(2-Deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3)-one-5'-monophosphate | 213131-44-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 3-(2-Deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3)-one-5'-monophosphate
• 英文别名: 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-a]purin-10(3H)-one 5'-monophosphate；3-(2'-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-a]purin-10(3H)-one 5'-phosphate；3-(2-Deoxy-beta-D-ribofuranosyl)-pyrido[5,6-A]-purine-10-one-5'-monophosphate；[(2R,3S,5R)-3-hydroxy-5-(10-oxopyrimido[1,2-a]purin-3-yl)oxolan-2-yl]methyl dihydrogen phosphate
• CAS: 213131-44-3
• 化学式: C₁₃H₁₄N₅O₇P
• 分子量: 383.257
• InChiKey: VHESJINRMVWRRK-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-(2-Deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3)-one-5'-monophosphate 在 phosphate buffer 作用下， 生成 N²-(3-oxoprop-1-enyl)deoxyguanosine 5'-phosphate sodium salt
  参考文献：
  名称：

  Kinetic and Thermodynamic Analysis of the Hydrolytic Ring-Opening of the Malondialdehyde−Deoxyguanosine Adduct, 3-(2‘-Deoxy-β-d-erythro-pentofuranosyl)- pyrimido[1,2-α]purin-10(3H)-one

  摘要：

  3-(2'- Deoxy-beta-D-erythro-pentofuranosyl) pyrimido[1,2-alpha]purin-10(3H)-one (M(1)dG) is the major reaction product of deoxyguanosine with malondialdehyde or base propenals. M(1)dG undergoes hydrolytic ring-opening to N-2-oxopropenyl-deoxyguanosine (N(2)OPdG) under basic conditions. We report that ring-opening of M(1)dG as a nucleoside or in oligonucleotides is a reversible second-order reaction with hydroxide ion. NMR and UV analysis revealed N(2)OPdG(-) to be the only product of M(1)dG ring-opening in basic solution. The rate constant for reaction of M1dG with hydroxide is 3.8 M-1 s(-1), and the equilibrium constant is calculated to be 2.1 +/- 0.3 x 10(4) M-1 at 25 degreesC. Equilibrium constants determined by spectroscopic analysis of the reaction end-point or by thermodynamic analysis of rate constants determined over a range of temperatures yielded a value 2.5 +/- 0.2 x 10(4) M-1. Kinetic analysis of ring-opening of M1dG in oligonucleotides indicated the rate constant for ring-opening is decreased 10-fold compared to that in the nucleoside. Flanking purines or pyrimidines did not significantly alter the rate constants for ring-opening, but purines flanking M1dG enhanced the rate constant for the reverse reaction. A mechanism is proposed for ring-opening of M(1)dG under basic conditions and a role is proposed for duplex DNA in accelerating the rate of ring-opening of M(1)dG at neutral pH.

  DOI：

  10.1021/ja040009r
• 作为产物：
  描述：

  N²-(3-oxoprop-1-enyl)deoxyguanosine 5'-phosphate sodium salt 在 phosphate buffer 作用下， 生成 3-(2-Deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3)-one-5'-monophosphate
  参考文献：
  名称：

  Kinetic and Thermodynamic Analysis of the Hydrolytic Ring-Opening of the Malondialdehyde−Deoxyguanosine Adduct, 3-(2‘-Deoxy-β-d-erythro-pentofuranosyl)- pyrimido[1,2-α]purin-10(3H)-one

  摘要：

  3-(2'- Deoxy-beta-D-erythro-pentofuranosyl) pyrimido[1,2-alpha]purin-10(3H)-one (M(1)dG) is the major reaction product of deoxyguanosine with malondialdehyde or base propenals. M(1)dG undergoes hydrolytic ring-opening to N-2-oxopropenyl-deoxyguanosine (N(2)OPdG) under basic conditions. We report that ring-opening of M(1)dG as a nucleoside or in oligonucleotides is a reversible second-order reaction with hydroxide ion. NMR and UV analysis revealed N(2)OPdG(-) to be the only product of M(1)dG ring-opening in basic solution. The rate constant for reaction of M1dG with hydroxide is 3.8 M-1 s(-1), and the equilibrium constant is calculated to be 2.1 +/- 0.3 x 10(4) M-1 at 25 degreesC. Equilibrium constants determined by spectroscopic analysis of the reaction end-point or by thermodynamic analysis of rate constants determined over a range of temperatures yielded a value 2.5 +/- 0.2 x 10(4) M-1. Kinetic analysis of ring-opening of M1dG in oligonucleotides indicated the rate constant for ring-opening is decreased 10-fold compared to that in the nucleoside. Flanking purines or pyrimidines did not significantly alter the rate constants for ring-opening, but purines flanking M1dG enhanced the rate constant for the reverse reaction. A mechanism is proposed for ring-opening of M(1)dG under basic conditions and a role is proposed for duplex DNA in accelerating the rate of ring-opening of M(1)dG at neutral pH.

  DOI：

  10.1021/ja040009r

文献信息

• Development of Monoclonal Antibodies to the Malondialdehyde−Deoxyguanosine Adduct, Pyrimidopurinone¹
  作者：Cynthia L. Sevilla、Norma H. Mahle、Naomi Eliezer、Adam Uzieblo、Shawn M. O'Hara、Munetaka Nokubo、Ryan Miller、Carol A. Rouzer、Lawrence J. Marnett

  DOI：10.1021/tx960120d

  日期：1997.2.1

  Malondialdehyde (MDA), an endogenous product of lipid peroxidation and prostaglandin biosynthesis, is mutagenic in bacterial and mammalian cells and carcinogenic in rats. In order to determine whether MDA-modified bases are formed in nucleic acids in vivo, sensitive immunoassays to detect MDA-DNA and MDA-RNA adducts are being developed in our laboratory. Murine monoclonal antibodies reactive with the MDA-deoxyguanosine adduct 3-beta-D-erythro-pentofuranosylpyrimido[1,2-alpha]purin-10(3H)-one (M(1)G-R) were prepared and characterized. Several MDA-modified nucleosides and deoxynucleosides and structural analogs were synthesized and characterized and were compared as competitive inhibitors in enzymelinked immunosorbent assays (ELISAs). Less than 5 fmol of M(1)G in MDA-modified DNA was detected in a direct ELISA, and antibody binding to the modified DNA was competitively inhibited by free M(1)G-dR. DNA from Salmonella typhimurium treated with concentrations of MDA that induce reversion to histidine prototrophy was enzymatically digested, and M(1)G-dR was quantitated by competitive ELISA. Over a range of MDA concentrations from 10 to 40 mM, the level of M(1)G residues in bacterial DNA increased from 0.2 to 2.5/10(6) base pairs.
• An Improved ³²P-Postlabeling/High-Performance Liquid Chromatography Method for the Analysis of the Malondialdehye-Derived 1,<i>N</i>²-Propanodeoxyguanosine DNA Adduct in Animal and Human Tissues
  作者：Ping Yi、Xin Sun、Daniel R. Doerge、Peter P. Fu

  DOI：10.1021/tx9800497

  日期：1998.9.1

  Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and tumorigenic. The MDA-modified DNA adduct, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)pyr [1,2-alpha]purin-10(3H)-one (M(1)G), has been detected in human tissues and may be a marker of human cancer risk. In this paper, we describe an improved P-32-postlabeling/HPLC method for sensitive detection and quantitation of this MDA-modified 2'-deoxyribonucleotide adduct. Specific improvements include (i) unequivocal structural identification of the postlabeling products, both the 3',5'-bisphosphate of M(1)G (MDA-3',5'-dGDP) and the 5'-monophosphate of M1G (MDA-5'-dGMP); (ii) efficient separation of the P-32-postlabeling products by HPLC; and (iii) the incorporation of a synthetically prepared MDA-modified DNA (or the 3'-monophosphate of M(1)G) with a known modification level as an internal standard. This improved quantitative methodology provides high intra- and inter-assay reproducibility and has been applied to the analysis of this adduct in rodent and human samples.
• Kinetic and Thermodynamic Analysis of the Hydrolytic Ring-Opening of the Malondialdehyde−Deoxyguanosine Adduct, 3-(2‘-Deoxy-β-<scp>d</scp>-<i>e</i><i>rythro</i>-pentofuranosyl)- pyrimido[1,2-α]purin-10(3<i>H</i>)-one
  作者：James N. Riggins、J. Scott Daniels、Carol A. Rouzer、Lawrence J. Marnett

  DOI：10.1021/ja040009r

  日期：2004.7.1

  3-(2'- Deoxy-beta-D-erythro-pentofuranosyl) pyrimido[1,2-alpha]purin-10(3H)-one (M(1)dG) is the major reaction product of deoxyguanosine with malondialdehyde or base propenals. M(1)dG undergoes hydrolytic ring-opening to N-2-oxopropenyl-deoxyguanosine (N(2)OPdG) under basic conditions. We report that ring-opening of M(1)dG as a nucleoside or in oligonucleotides is a reversible second-order reaction with hydroxide ion. NMR and UV analysis revealed N(2)OPdG(-) to be the only product of M(1)dG ring-opening in basic solution. The rate constant for reaction of M1dG with hydroxide is 3.8 M-1 s(-1), and the equilibrium constant is calculated to be 2.1 +/- 0.3 x 10(4) M-1 at 25 degreesC. Equilibrium constants determined by spectroscopic analysis of the reaction end-point or by thermodynamic analysis of rate constants determined over a range of temperatures yielded a value 2.5 +/- 0.2 x 10(4) M-1. Kinetic analysis of ring-opening of M1dG in oligonucleotides indicated the rate constant for ring-opening is decreased 10-fold compared to that in the nucleoside. Flanking purines or pyrimidines did not significantly alter the rate constants for ring-opening, but purines flanking M1dG enhanced the rate constant for the reverse reaction. A mechanism is proposed for ring-opening of M(1)dG under basic conditions and a role is proposed for duplex DNA in accelerating the rate of ring-opening of M(1)dG at neutral pH.