Thioacetic acid S-[(2S,3S,5R)-5-(6-amino-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester | 184229-70-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 2 '，5'-二脱氧核苷
• 英文名称: Thioacetic acid S-[(2S,3S,5R)-5-(6-amino-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester
• CAS: 184229-70-7
• 化学式: C₁₂H₁₅N₅O₃S
• 分子量: 309.349
• InChiKey: HQJSIEPPOZTSTM-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.34
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  116.15
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  Thioacetic acid S-[(2S,3S,5R)-5-(6-amino-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester 在 吡啶 、 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 吡啶 、 乙醇 、 二氯甲烷 为溶剂， 反应 14.12h， 生成 N-{9-[(2R,4S,5S)-5-({[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}methyl)-4-({[bis(propan-2-yl)amino](2-cyanoethoxy)phosphanyl}oxy)oxolan-2-yl]-9H-purin-6-yl}benzamide
  参考文献：
  名称：

  Alteration of DNA Primary Structure by DNA Topoisomerase I. Isolation of the Covalent Topoisomerase I−DNA Binary Complex in Enzymatically Competent Form

  摘要：

  DNA ligation by DNA topoisomerase I was investigated employing synthetic DNA substrates containing a single strand nick. Site-specific cleavage of the DNA by topoisomerase I in proximity to the nick resulted in uncoupling of the cleavage and ligation reactions of the enzyme, thereby trapping the covalent enzyme-DNA intermediate. DNA cleavage could be reversed by the addition of acceptor oligonucleotides containing a free 5'-OH group and capable of hybridizing to the noncleaved strand of the ''suicide substrates''. Utilizing accepters with partial complementarity, modification of nucleic acid structure has been obtained. Modifications included the formation of DNA insertions, deletions, and mismatches. To further evaluate the potential of topoisomerase I to mediate structural transformations of DNA, acceptor oligonucleotides containing nucleophiles other than OH groups at the 5'-end were studied as substrates for the topoisomerase I-mediated ligation reaction. Toward this end, oligonucleotides containing 5'-thio, amino, and hydroxymethylene moieties were synthesized. Initial investigations utilizing a coupled cleavage-ligation assay suggested that only the modified acceptor containing an additional methylene group underwent efficient enzyme-mediated ligation. However, as linear DNA is not a preferred substrate for topoisomerase I, the enzyme-DNA intermediate was purified to homogeneity, thereby allowing investigation of the ligation reaction independent of the forward reaction that formed the covalent binary complex. The isolated complex consisted of equimolar enzyme and DNA, with topoisomerase I covalently bound to a specific site on the DNA duplex in an enzymatically competent form. Displacement of the enzyme-linked tyrosine moiety of the enzyme-DNA binary complex was effected by all the modified acceptor oligonucleotides, affording unnatural internucleosidic linkages at a specific site. Characterization of the formed linkages was effected both by enzymatic and chemical degradation studies. Comparative analysis revealed overall differences in the efficiency and rate of the topoisomerase I-mediated ligation of the modified acceptors. Moreover, the facility of ligation of the amino acceptor was significantly enhanced at increasing pH values. In addition, the method utilized to obtain the topoisomerase I-DNA intermediate is capable of affording large quantities required for further mechanistic and physicochemical characterization of the formed binary complex.

  DOI：

  10.1021/ja961788h
• 作为产物：
  描述：

  硫代乙酸 、 2'-脱氧腺苷 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以88%的产率得到Thioacetic acid S-[(2S,3S,5R)-5-(6-amino-purin-9-yl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester
  参考文献：
  名称：

  Alteration of DNA Primary Structure by DNA Topoisomerase I. Isolation of the Covalent Topoisomerase I−DNA Binary Complex in Enzymatically Competent Form

  摘要：

  DNA ligation by DNA topoisomerase I was investigated employing synthetic DNA substrates containing a single strand nick. Site-specific cleavage of the DNA by topoisomerase I in proximity to the nick resulted in uncoupling of the cleavage and ligation reactions of the enzyme, thereby trapping the covalent enzyme-DNA intermediate. DNA cleavage could be reversed by the addition of acceptor oligonucleotides containing a free 5'-OH group and capable of hybridizing to the noncleaved strand of the ''suicide substrates''. Utilizing accepters with partial complementarity, modification of nucleic acid structure has been obtained. Modifications included the formation of DNA insertions, deletions, and mismatches. To further evaluate the potential of topoisomerase I to mediate structural transformations of DNA, acceptor oligonucleotides containing nucleophiles other than OH groups at the 5'-end were studied as substrates for the topoisomerase I-mediated ligation reaction. Toward this end, oligonucleotides containing 5'-thio, amino, and hydroxymethylene moieties were synthesized. Initial investigations utilizing a coupled cleavage-ligation assay suggested that only the modified acceptor containing an additional methylene group underwent efficient enzyme-mediated ligation. However, as linear DNA is not a preferred substrate for topoisomerase I, the enzyme-DNA intermediate was purified to homogeneity, thereby allowing investigation of the ligation reaction independent of the forward reaction that formed the covalent binary complex. The isolated complex consisted of equimolar enzyme and DNA, with topoisomerase I covalently bound to a specific site on the DNA duplex in an enzymatically competent form. Displacement of the enzyme-linked tyrosine moiety of the enzyme-DNA binary complex was effected by all the modified acceptor oligonucleotides, affording unnatural internucleosidic linkages at a specific site. Characterization of the formed linkages was effected both by enzymatic and chemical degradation studies. Comparative analysis revealed overall differences in the efficiency and rate of the topoisomerase I-mediated ligation of the modified acceptors. Moreover, the facility of ligation of the amino acceptor was significantly enhanced at increasing pH values. In addition, the method utilized to obtain the topoisomerase I-DNA intermediate is capable of affording large quantities required for further mechanistic and physicochemical characterization of the formed binary complex.

  DOI：

  10.1021/ja961788h