grassystatin C | 1187551-30-9

• 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 C
• 英文别名: methyl (2S)-1-[(2R)-2-[[2-[[(2S,3S)-2-[[(3S,4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2R,3S)-2-hydroxy-3-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-5-oxopentanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate
• CAS: 1187551-30-9
• 化学式: C₅₀H₈₂N₈O₁₂
• 分子量: 987.247
• InChiKey: CRTPOZWNLFMWPB-YQGVOMCUSA-N

物化性质

• 沸点：
  1200.8±65.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  70
• 可旋转键数：
  30
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  287
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  grassystatin C 在 盐酸 、 水 作用下， 反应 24.0h， 生成 L-亮氨酸 、 L-异亮氨酸 、 (2R,3S)-2-羟基-3-甲基戊酸 、 N-methyl-L-glutamic acid 、 N-甲基-D-苯丙氨酸 、 L-脯氨酸
  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

文献信息

• PROTEASE INHIBITORS, COMPOSITIONS AND METHODS OF USE
  申请人：Luesch Hendrik

  公开号：US20120178669A1

  公开（公告）日：2012-07-12

  This invention relates to grassystatins A, B and C, and their isolated or purified forms. The compounds of the invention are useful as aspartic protease, gamma secretase, or metalloprotease inhibitors. Methods of using the compounds and compositions thereof are also disclosed.

  本发明涉及草酸酯素A、B和C及其分离或纯化形式。本发明的化合物可用作天冬氨酸蛋白酶、γ-分泌酶或金属蛋白酶抑制剂。本发明还揭示了使用这些化合物和其组合物的方法。
• Protease inhibitors, compositions and methods of use
  申请人：Luesch Hendrik

  公开号：US08569245B2

  公开（公告）日：2013-10-29

  This invention relates to grassystatins A, B and C, and their isolated or purified forms. The compounds of the invention are useful as aspartic protease, gamma secretase, or metalloprotease inhibitors. Methods of using the compounds and compositions thereof are also disclosed.

  本发明涉及草酸素A、B和C及其分离或纯化形式。本发明的化合物可用作天冬氨酸蛋白酶、γ-分泌酶或金属蛋白酶抑制剂。还公开了使用这些化合物和其组合物的方法。
• [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