phaeofungin | 1416512-73-6

• 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: phaeofungin
• 英文别名: cyclo-[DHMHDA-L-Ser-D-Ala-D-Asp-L-Ala-D-Ser-D-Ser-D-allo-Thr]；Phaeofungin；2-[(3R,6R,9R,12S,15R,18R,21S)-3-[(1R)-1-hydroxyethyl]-6,9,21-tris(hydroxymethyl)-25-(2-hydroxytetradecan-2-yl)-12,18-dimethyl-2,5,8,11,14,17,20,23-octaoxo-1-oxa-4,7,10,13,16,19,22-heptazacyclopentacos-15-yl]acetic acid
• CAS: 1416512-73-6
• 化学式: C₄₀H₆₉N₇O₁₆
• 分子量: 904.025
• InChiKey: WKSAMKWFSYJCOB-YRHXLCEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  63
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  368
• 氢给体数：
  13
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  phaeofungin 在 水 、 sodium hydroxide 作用下， 反应 1.5h， 生成 (3R)-4-[[(2S)-1-[[(2R)-1-[[(2R)-1-[[(1R,2R)-1-carboxy-2-hydroxypropyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2R)-2-[[(2S)-2-[(3,4-dihydroxy-4-methylhexadecanoyl)amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-4-oxobutanoic acid
  参考文献：
  名称：

  Isolation, Structure, and Biological Activity of Phaeofungin, a Cyclic Lipodepsipeptide from aPhaeosphaeriasp. Using the Genome-WideCandida albicansFitness Test

  摘要：

  Phaeofungin (1), a new cyclic depsipeptide isolated from Phaeosphaeria sp., was discovered by application of reverse genetics technology, using the Candida albicans fitness test (CaFT). Phaeofungin is comprised of seven amino acids and a beta,gamma-dihydroxy-gamma-methylhexadecanoic acid arranged in a 25-membered cyclic depsipeptide. Five of the amino acids were assigned with D-configurations. The structure was elucidated by 2D-NMR and HRMS-MS analysis of the natural product and its hydrolyzed linear peptide. The absolute configuration of the amino acids was determined by Marfey's method by complete and partial hydrolysis of 1. The CaFT profile of the phaeofungin-containing extract overlapped with that of phomafungin (3), another structurally different cyclic lipodepsipeptide isolated from a Phoma sp. using the same approach. Comparative biological characterization further demonstrated that these two fungal lipodepsipeptides are functionally distinct. While phomafungin was potentiated by cyclosporin A (an inhibitor of the calcineurin pathway), phaeofungin was synergized with aureobasidin A (2) (an inhibitor of the sphingolipid biosynthesis) and to some extent caspofungin (an inhibitor of glucan synthase). Furthermore, phaeofiingin caused ATP release in wild-type C. albicans strains but phomafungin did not. It showed modest antifungal activity against C. albicans (MIC 16-32 mu g/mL) and better activity against Aspergillus fumigatus (MIC 8-16 mu g/mL) and Trichophyton mentagrophytes (MIC 4 mu g/mL). The linear peptide was inactive, suggesting that the macrocyclic depsipeptide ring is essential for target engagement and antifungal activity.

  DOI：

  10.1021/np300704s

文献信息

• Isolation, Structure, and Biological Activity of Phaeofungin, a Cyclic Lipodepsipeptide from a<i>Phaeosphaeria</i>sp. Using the Genome-Wide<i>Candida albicans</i>Fitness Test
  作者：Sheo B. Singh、John Ondeyka、Guy Harris、Kithsiri Herath、Deborah Zink、Francisca Vicente、Gerald Bills、Javier Collado、Gonzalo Platas、Antonio González del Val、Jesus Martin、Fernando Reyes、Hao Wang、Jennifer Nielsen Kahn、Stefan Galuska、Robert Giacobbe、George Abruzzo、Terry Roemer、Deming Xu

  DOI：10.1021/np300704s

  日期：2013.3.22

  Phaeofungin (1), a new cyclic depsipeptide isolated from Phaeosphaeria sp., was discovered by application of reverse genetics technology, using the Candida albicans fitness test (CaFT). Phaeofungin is comprised of seven amino acids and a beta,gamma-dihydroxy-gamma-methylhexadecanoic acid arranged in a 25-membered cyclic depsipeptide. Five of the amino acids were assigned with D-configurations. The structure was elucidated by 2D-NMR and HRMS-MS analysis of the natural product and its hydrolyzed linear peptide. The absolute configuration of the amino acids was determined by Marfey's method by complete and partial hydrolysis of 1. The CaFT profile of the phaeofungin-containing extract overlapped with that of phomafungin (3), another structurally different cyclic lipodepsipeptide isolated from a Phoma sp. using the same approach. Comparative biological characterization further demonstrated that these two fungal lipodepsipeptides are functionally distinct. While phomafungin was potentiated by cyclosporin A (an inhibitor of the calcineurin pathway), phaeofungin was synergized with aureobasidin A (2) (an inhibitor of the sphingolipid biosynthesis) and to some extent caspofungin (an inhibitor of glucan synthase). Furthermore, phaeofiingin caused ATP release in wild-type C. albicans strains but phomafungin did not. It showed modest antifungal activity against C. albicans (MIC 16-32 mu g/mL) and better activity against Aspergillus fumigatus (MIC 8-16 mu g/mL) and Trichophyton mentagrophytes (MIC 4 mu g/mL). The linear peptide was inactive, suggesting that the macrocyclic depsipeptide ring is essential for target engagement and antifungal activity.