8-[(3-methyl-3H-naphtho[2,1-d]imidazol-2-yl)amino]-2'-desoxyguanosine | 1224969-47-4

• 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: 8-[(3-methyl-3H-naphtho[2,1-d]imidazol-2-yl)amino]-2'-desoxyguanosine
• CAS: 1224969-47-4
• 化学式: C₂₂H₂₂N₈O₄
• 分子量: 462.468
• InChiKey: LXXMVZDEHKJWOG-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.13
• 重原子数：
  34.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  169.13
• 氢给体数：
  5.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  8-[(3-methyl-3H-naphtho[2,1-d]imidazol-2-yl)amino]-2'-desoxyguanosine 、 N,N-二甲基甲酰胺二乙基缩醛 以 甲醇 为溶剂， 反应 2.0h， 以83%的产率得到N2-[(dimethylamino)methylene]-8-[(3-methyl-3H-naphtho[2,1-d]imidazol-2-yl)amino]-N9-[β-D-2'-desoxyribofuranosyl]guanine
  参考文献：
  名称：

  The C8-2′-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[1,2-d]naphthalene, a Carbocyclic Analogue of the Potent Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline, Is a Block to Replication in Vitro

  摘要：

  2-Amino-3-methylimidazo[1,2-d]naphthalene (cIQ) is a carbocyclic analogue of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in which a naphthalene ring system replaces the quinoline unit of IQ. The activity of cIQ in Ames Salmonella typhimurium tester strain TA98 is known to be 4-5 orders of magnitude lower than IQ. cIQ undergoes efficient bioactivation with rat liver microsomes. The C8-dGuo adduct was formed when calf thymus DNA was treated with the N-hydroxy-cIQ metabolite and either acetic anhydride or extracts from cells that overexpress N-acetyl transferase (NAT). These studies indicate that bioactivation, the stability of the N-hydroxylamine ester, and the reactivity of the nitrenium ion with DNA of cIQ are similar to IQ and that none of these factors account for the differences in mutagenic potency of these analogues in Ames assays. Oligonucleotides were synthesized that contain the C8-dGuo adduct of cIQ in the frameshift-prone CG-dinucleotide repeat unit of the Narl recognition sequence. We have examined the in vitro translesion synthesis of this adduct and have found it to be a strong replication block to Escherichia coli DNA polymerase I, Klenow fragment exo(-) (Kf(-)), E. coli DNA polymerase II exo(-) (pol II-), and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Previous studies by Fuchs and co-workers identified E. coli pol II as the polymerase responsible for two-base deletions of the C8-dGuo adduct of N-acetyl-2-aminofluorene in the Narl sequence. Our observation that pol II is strongly inhibited by the C8-dGuo adduct of cIQ suggests that one of the other SOS inducible polymerases (E. coli pol IV or pol V) is required for its bypass, and this accounts for the greatly attenuated mutagenicity in the Ames assays as compared with IQ.

  DOI：

  10.1021/tx100053n
• 作为产物：
  描述：

  8-[(3-methyl-3H-naphtho[2,1-d]imidazol-2-yl)amino]-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-β-D-2'-desoxyribofuranosyl]guanine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以93%的产率得到8-[(3-methyl-3H-naphtho[2,1-d]imidazol-2-yl)amino]-2'-desoxyguanosine
  参考文献：
  名称：

  The C8-2′-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[1,2-d]naphthalene, a Carbocyclic Analogue of the Potent Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline, Is a Block to Replication in Vitro

  摘要：

  2-Amino-3-methylimidazo[1,2-d]naphthalene (cIQ) is a carbocyclic analogue of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in which a naphthalene ring system replaces the quinoline unit of IQ. The activity of cIQ in Ames Salmonella typhimurium tester strain TA98 is known to be 4-5 orders of magnitude lower than IQ. cIQ undergoes efficient bioactivation with rat liver microsomes. The C8-dGuo adduct was formed when calf thymus DNA was treated with the N-hydroxy-cIQ metabolite and either acetic anhydride or extracts from cells that overexpress N-acetyl transferase (NAT). These studies indicate that bioactivation, the stability of the N-hydroxylamine ester, and the reactivity of the nitrenium ion with DNA of cIQ are similar to IQ and that none of these factors account for the differences in mutagenic potency of these analogues in Ames assays. Oligonucleotides were synthesized that contain the C8-dGuo adduct of cIQ in the frameshift-prone CG-dinucleotide repeat unit of the Narl recognition sequence. We have examined the in vitro translesion synthesis of this adduct and have found it to be a strong replication block to Escherichia coli DNA polymerase I, Klenow fragment exo(-) (Kf(-)), E. coli DNA polymerase II exo(-) (pol II-), and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Previous studies by Fuchs and co-workers identified E. coli pol II as the polymerase responsible for two-base deletions of the C8-dGuo adduct of N-acetyl-2-aminofluorene in the Narl sequence. Our observation that pol II is strongly inhibited by the C8-dGuo adduct of cIQ suggests that one of the other SOS inducible polymerases (E. coli pol IV or pol V) is required for its bypass, and this accounts for the greatly attenuated mutagenicity in the Ames assays as compared with IQ.

  DOI：

  10.1021/tx100053n