grassystatin A | 1187551-28-5

• 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: grassystatin A
• 英文别名: methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-2-[[(3S,4S)-4-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[(2S)-2-[(2S)-2-(dimethylamino)-3-methylbutanoyl]oxy-3-methylbutanoyl]oxy-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate
• CAS: 1187551-28-5
• 化学式: C₅₈H₉₅N₉O₁₆
• 分子量: 1174.44
• InChiKey: JZYWSTGTBRHGTL-BIXXXADNSA-N

物化性质

• 沸点：
  1289.4±65.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  83
• 可旋转键数：
  36
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  352
• 氢给体数：
  8
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  grassystatin A 在 甲醇 、 sodium hydroxide 作用下， 反应 72.0h， 生成 D-α-羟基异戊酸 、 L-α-羟基异戊酸
  参考文献：
  名称：

  Grassystatins A−C from Marine Cyanobacteria, Potent Cathepsin E Inhibitors That Reduce Antigen Presentation

  摘要：

  In our efforts to explore marine cyanobacteria as a source of novel bioactive compounds, we discovered a statine unit-containing linear decadepsipeptide, grassystatin A (1), which we screened against a diverse set of 59 proteases. We describe the structure determination of I and two natural analogues, grassystatins B (2) and C (3), using NMR, MS, and chiral HPLC techniques. Compound I selectively inhibited cathepsins D and E with IC50S of 26.5 nM and 886 pM, respectively. Compound 2 showed similar potency and selectivity against cathepsins D and E (IC50S of 7.27 nM and 354 pM, respectively), whereas the truncated peptide analogue grassystatin C (3), which consists of two fewer residues than I and 2, was less potent against both but still selective for cathepsin E. The selectivity of compounds 1-3 for cathepsin E over D (20-38-fold) suggests that these natural products may be useful tools to probe cathepsin E function. We investigated the structural basis of this selectivity using molecular docking. We also show that I can reduce antigen presentation by dendritic cells, a process thought to rely on cathepsin E.

  DOI：

  10.1021/jm9009394
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-N-methyl-D-phenylalanine 在 N-羟基-7-氮杂苯并三氮唑 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 48.65h， 生成 grassystatin A
  参考文献：
  名称：

  Total synthesis of grassystatin A, a probe for cathepsin E function

  摘要：

  The linear depsipeptide grassystatin A, a valuable probe for the study of cathepsin E function, has been synthesized by a [4+6] strategy. It exhibited specific inhibitory activity against cathepsin E with an IC50 value of 0.8 nM. Our studies indicated that inhibition of cathepsin E did not have an impact on ovalbumin antigen processing and peptide presentation, unique from studies of other aspartic protease inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.077

文献信息

• [EN] PROTEASE INHIBITORS, COMPOSITIONS AND METHODS OF USE<br/>[FR] INHIBITEURS DE LA PROTÉASE, COMPOSITIONS LES COMPRENANT ET PROCÉDÉS D'UTILISATION
  申请人：UNIV FLORIDA

  公开号：WO2010151852A3

  公开（公告）日：2011-08-04
• Total synthesis of grassystatin A, a probe for cathepsin E function
  作者：Siming Yang、Wei Zhang、Ning Ding、Jeannette Lo、Yanxia Liu、Michael J. Clare-Salzler、Hendrik Luesch、Yingxia Li

  DOI：10.1016/j.bmc.2012.05.077

  日期：2012.8

  The linear depsipeptide grassystatin A, a valuable probe for the study of cathepsin E function, has been synthesized by a [4+6] strategy. It exhibited specific inhibitory activity against cathepsin E with an IC50 value of 0.8 nM. Our studies indicated that inhibition of cathepsin E did not have an impact on ovalbumin antigen processing and peptide presentation, unique from studies of other aspartic protease inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.
• Grassystatins A−C from Marine Cyanobacteria, Potent Cathepsin E Inhibitors That Reduce Antigen Presentation
  作者：Jason C. Kwan、Erika A. Eksioglu、Chen Liu、Valerie J. Paul、Hendrik Luesch

  DOI：10.1021/jm9009394

  日期：2009.9.24

  In our efforts to explore marine cyanobacteria as a source of novel bioactive compounds, we discovered a statine unit-containing linear decadepsipeptide, grassystatin A (1), which we screened against a diverse set of 59 proteases. We describe the structure determination of I and two natural analogues, grassystatins B (2) and C (3), using NMR, MS, and chiral HPLC techniques. Compound I selectively inhibited cathepsins D and E with IC50S of 26.5 nM and 886 pM, respectively. Compound 2 showed similar potency and selectivity against cathepsins D and E (IC50S of 7.27 nM and 354 pM, respectively), whereas the truncated peptide analogue grassystatin C (3), which consists of two fewer residues than I and 2, was less potent against both but still selective for cathepsin E. The selectivity of compounds 1-3 for cathepsin E over D (20-38-fold) suggests that these natural products may be useful tools to probe cathepsin E function. We investigated the structural basis of this selectivity using molecular docking. We also show that I can reduce antigen presentation by dendritic cells, a process thought to rely on cathepsin E.