H-Thr(1)-D-Val-Pro-Sar-N(Me)Val-(1)

• 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: H-Thr(1)-D-Val-Pro-Sar-N(Me)Val-(1)
• 英文别名: (3R,6S,7R,10S,16S)-6-amino-7,11,14-trimethyl-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecane-2,5,9,12,15-pentone
• 化学式: C₂₃H₃₉N₅O₆
• 分子量: 481.593
• InChiKey: BBYIXLRFQJBTBG-QDSNELGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  H-Thr(1)-D-Val-Pro-Sar-N(Me)Val-(1) 在 钯 氢气 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 3.0h， 生成 (3-hydroxy-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone
  参考文献：
  名称：

  Studies on 2-Aziridinecarboxylic Acid. VIII. Total Synthesis of Actinomycin D and Its Serine AnalogueviaRing-opening Reaction of 1-Benzyloxycarbonyl-2-aziridinecarboxylic Acid Moiety

  摘要：

  通过β-羟基-α-氨基酸肽与DEAD-TPP试剂的反应，直接合成了含有1-苄氧羰基-2-氮丙啶羧酸的肽，并通过氮丙啶与N-保护二肽的开环反应，制备了放线菌素D合成的关键O肽中间体。用 DCC-HOBt 法制备了肽内酯，随后的去苄基程序和氧化程序以良好的收率得到了标题化合物。

  DOI：

  10.1246/bcsj.55.3237
• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-D-valylprolylsarcosine tert-butyl ester 在 palladium on activated charcoal 4-二甲氨基吡啶 、 N,N-bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， -10.0~25.0 ℃ 、101.33 kPa 条件下， 反应 142.0h， 生成 H-Thr(1)-D-Val-Pro-Sar-N(Me)Val-(1)
  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