1-{O⁴-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)thymidinyl]}-7-{O6-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)-N²-phenoxyacetyl-2'-deoxyguanosinyl]}heptane | 1421765-84-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-{O⁴-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)thymidinyl]}-7-{O6-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)-N²-phenoxyacetyl-2'-deoxyguanosinyl]}heptane
• CAS: 1421765-84-5
• 化学式: C₈₉H₁₀₉N₇O₁₅Si₂
• 分子量: 1573.05
• InChiKey: PNBMSEZXHUECGK-IJSFVCLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  17.52
• 重原子数：
  113.0
• 可旋转键数：
  36.0
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  227.58
• 氢给体数：
  1.0
• 氢受体数：
  21.0

反应信息

• 作为反应物：
  描述：

  1-{O⁴-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)thymidinyl]}-7-{O6-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)-N²-phenoxyacetyl-2'-deoxyguanosinyl]}heptane 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以95%的产率得到1-{O⁴-[5′-O-(4,4′-dimethoxytrityl)thymidinyl]}-7-{O6-[5'-O-(4,4′-dimethoxytrityl)-N²-phenoxyacetyl-2′-deoxyguanosinyl]}heptane
  参考文献：
  名称：

  Preparation of Covalently Linked Complexes Between DNA and O⁶-Alkylguanine-DNA Alkyltransferase Using Interstrand Cross-Linked DNA

  摘要：

  O-6-alkylguanine-DNA alkyltransferases (AGT) are responsible for the removal of alkylation at both the O-6 atom of guanine and O-4 atom of thymine. AGT homologues show vast substrate differences with respect to the size of the adduct and which alkylated atoms they can restore. The human AGT (hAGT) has poor capabilities for removal of methylation at the O-4 atom of thymidine, which is not the case in most homologues. No structural data are available to explain this poor hAGT repair. We prepared and characterized O(6)G-butylene-(OT)-T-4 (XLGT4) and O(6)G-heptylene-(OT)-T-4 (XLGT7) interstrand cross-linked (ICL) DNA as probes for hAGT and the Escherichia coli homologues, OCT and Ada-C, for the formation of DNA-ACT covalent complexes. XLGT7 reacted only with hAGT and did so with a cross-linking efficiency of 25%, while XLGT4 was inert to all ACT tested. The hAGT mediated repair of XLGT7 occurred slowly, on the order of hours as opposed to the repair of O-6-methyl-2'-deoxyguanosine which requires seconds. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the repair reaction revealed the formation of a covalent complex with an observed migration in accordance with a DNA-ACT complex. The identity of this covalent complex, as determined by mass spectrometry, was composed of a heptamethylene bridge between the O-4 atom of thymidine (in an 11-mer DNA strand) to residue Cys145 of hAGT. This procedure can be applied to produce well-defined covalent complexes between ACT with DNA.

  DOI：

  10.1021/bc300553u
• 作为产物：
  描述：

  5'-O-dimethoxytrityl-3'-O-t-butyldimethylsilyl-N²-(phenoxyacetyl)-2′-deoxyguanosine 、 5'-O-dimethoxytrityl-3'-O-t-butyldimethylsilyl-O⁴-(hydroxyheptyl)thymidine 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 22.0h， 以70%的产率得到1-{O⁴-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)thymidinyl]}-7-{O6-[3′-O-(t-butyldimethylsilyl)-5′-O-(4,4′-dimethoxytrityl)-N²-phenoxyacetyl-2'-deoxyguanosinyl]}heptane
  参考文献：
  名称：

  Preparation of Covalently Linked Complexes Between DNA and O⁶-Alkylguanine-DNA Alkyltransferase Using Interstrand Cross-Linked DNA

  摘要：

  O-6-alkylguanine-DNA alkyltransferases (AGT) are responsible for the removal of alkylation at both the O-6 atom of guanine and O-4 atom of thymine. AGT homologues show vast substrate differences with respect to the size of the adduct and which alkylated atoms they can restore. The human AGT (hAGT) has poor capabilities for removal of methylation at the O-4 atom of thymidine, which is not the case in most homologues. No structural data are available to explain this poor hAGT repair. We prepared and characterized O(6)G-butylene-(OT)-T-4 (XLGT4) and O(6)G-heptylene-(OT)-T-4 (XLGT7) interstrand cross-linked (ICL) DNA as probes for hAGT and the Escherichia coli homologues, OCT and Ada-C, for the formation of DNA-ACT covalent complexes. XLGT7 reacted only with hAGT and did so with a cross-linking efficiency of 25%, while XLGT4 was inert to all ACT tested. The hAGT mediated repair of XLGT7 occurred slowly, on the order of hours as opposed to the repair of O-6-methyl-2'-deoxyguanosine which requires seconds. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the repair reaction revealed the formation of a covalent complex with an observed migration in accordance with a DNA-ACT complex. The identity of this covalent complex, as determined by mass spectrometry, was composed of a heptamethylene bridge between the O-4 atom of thymidine (in an 11-mer DNA strand) to residue Cys145 of hAGT. This procedure can be applied to produce well-defined covalent complexes between ACT with DNA.

  DOI：

  10.1021/bc300553u