N8-actinomycin D

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N8-actinomycin D
• 英文别名: 8-amino-4,6-dimethyl-7-oxo-1-N,9-N-bis[(3R,6S,7R,10S,16S)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]pyrido[4,3-b][1,4]benzoxazine-1,9-dicarboxamide
• 化学式: C₆₁H₈₅N₁₃O₁₆
• 分子量: 1256.42
• InChiKey: DVAQENANCBGZCP-DKRVMSHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  90
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  368
• 氢给体数：
  5
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  (3-(benzyloxy)-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone 在 palladium on activated charcoal acetate buffer 、 氢气 、 potassium hexacyanoferrate(III) 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 N8-actinomycin D
  参考文献：
  名称：

  Toward the Design of an RNA:DNA Hybrid Binding Agent

  摘要：

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.

  DOI：

  10.1021/ja00085a002