myristoyl-(S)-Asn-(S)-Gln-OH | 1314527-54-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: myristoyl-(S)-Asn-(S)-Gln-OH
• 英文别名: (2S)-5-amino-2-[[(2S)-4-amino-4-oxo-2-(tetradecanoylamino)butanoyl]amino]-5-oxopentanoic acid
• CAS: 1314527-54-2
• 化学式: C₂₃H₄₂N₄O₆
• 分子量: 470.61
• InChiKey: COVKDYGTSBJYHH-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  182
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  myristoyl-(S)-Asn-(S)-Gln-OH 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三氧化硫吡啶 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 myristoyl-(S)-Asn-(S)-Gln-(S)-leucinal
  参考文献：
  名称：

  Isolation, Structure, and Biological Activities of Fellutamides C and D from an Undescribed Metulocladosporiella (Chaetothyriales) Using the Genome-Wide Candida albicans Fitness Test

  摘要：

  In a whole-cell mechanism of action (MOA)-based screening strategy for discovery of antifungal agents, Candida albicans was used followed by testing of active extracts in the C albicans fitness test (CaFT), which provides insight into the mechanism of action. A fermentation extract of an undescribed species of Metulocladosporiella that inhibited proteasome activity in a C. albicans fitness test was identified. The chemical genomic profile of the extract contained hypersensitivity of heterozygous deletion strains (strains that had one of the genes of the diploid genes knocked down) of genes represented by multiple subunits of the 25S proteasome. Two structurally related peptide aldehydes, named fellutamides C and D, were isolated from the extract. Fellutamides were active against C. albicans and Aspergillus fumigatus with MICs ranging from 4 to 16 mu g/mL and against fungal proteasome (IC50 0.2 mu g/mL). Both compounds showed proteasome activity against human tumor cell lines, potently inhibiting the growth of PC-3 prostate carcinoma cells, but not A549 lung carcinoma cells. In PC-3 cells compound treatment produced a G2M cell cycle block and induced apoptosis. Preliminary SAR studies indicated that the aldehyde group is critical for the antifungal activity and that the two hydroxy groups are quantitatively important for potency.

  DOI：

  10.1021/np2001573
• 作为产物：
  描述：

  L-谷氨酰胺叔丁酯 在 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 myristoyl-(S)-Asn-(S)-Gln-OH
  参考文献：
  名称：

  Isolation, Structure, and Biological Activities of Fellutamides C and D from an Undescribed Metulocladosporiella (Chaetothyriales) Using the Genome-Wide Candida albicans Fitness Test

  摘要：

  In a whole-cell mechanism of action (MOA)-based screening strategy for discovery of antifungal agents, Candida albicans was used followed by testing of active extracts in the C albicans fitness test (CaFT), which provides insight into the mechanism of action. A fermentation extract of an undescribed species of Metulocladosporiella that inhibited proteasome activity in a C. albicans fitness test was identified. The chemical genomic profile of the extract contained hypersensitivity of heterozygous deletion strains (strains that had one of the genes of the diploid genes knocked down) of genes represented by multiple subunits of the 25S proteasome. Two structurally related peptide aldehydes, named fellutamides C and D, were isolated from the extract. Fellutamides were active against C. albicans and Aspergillus fumigatus with MICs ranging from 4 to 16 mu g/mL and against fungal proteasome (IC50 0.2 mu g/mL). Both compounds showed proteasome activity against human tumor cell lines, potently inhibiting the growth of PC-3 prostate carcinoma cells, but not A549 lung carcinoma cells. In PC-3 cells compound treatment produced a G2M cell cycle block and induced apoptosis. Preliminary SAR studies indicated that the aldehyde group is critical for the antifungal activity and that the two hydroxy groups are quantitatively important for potency.

  DOI：

  10.1021/np2001573

文献信息

• Isolation, Structure, and Biological Activities of Fellutamides C and D from an Undescribed <i>Metulocladosporiella</i> (Chaetothyriales) Using the Genome-Wide <i>Candida albicans</i> Fitness Test
  作者：Deming Xu、John Ondeyka、Guy H. Harris、Deborah Zink、Jennifer Nielsen Kahn、Hao Wang、Gerald Bills、Gonzalo Platas、Wenxian Wang、Alexander A. Szewczak、Paul Liberator、Terry Roemer、Sheo B. Singh

  DOI：10.1021/np2001573

  日期：2011.8.26

  In a whole-cell mechanism of action (MOA)-based screening strategy for discovery of antifungal agents, Candida albicans was used followed by testing of active extracts in the C albicans fitness test (CaFT), which provides insight into the mechanism of action. A fermentation extract of an undescribed species of Metulocladosporiella that inhibited proteasome activity in a C. albicans fitness test was identified. The chemical genomic profile of the extract contained hypersensitivity of heterozygous deletion strains (strains that had one of the genes of the diploid genes knocked down) of genes represented by multiple subunits of the 25S proteasome. Two structurally related peptide aldehydes, named fellutamides C and D, were isolated from the extract. Fellutamides were active against C. albicans and Aspergillus fumigatus with MICs ranging from 4 to 16 mu g/mL and against fungal proteasome (IC50 0.2 mu g/mL). Both compounds showed proteasome activity against human tumor cell lines, potently inhibiting the growth of PC-3 prostate carcinoma cells, but not A549 lung carcinoma cells. In PC-3 cells compound treatment produced a G2M cell cycle block and induced apoptosis. Preliminary SAR studies indicated that the aldehyde group is critical for the antifungal activity and that the two hydroxy groups are quantitatively important for potency.