¹Gly-Arg-Cys(²)-Thr-Arg-Ser-Ile-Pro-Pro-Ile-Cys(²)-Phe-Pro-Asp¹

• 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: ¹Gly-Arg-Cys(²)-Thr-Arg-Ser-Ile-Pro-Pro-Ile-Cys(²)-Phe-Pro-Asp¹
• 英文别名: cyclo[Arg-Cys(1)-Thr-Arg-Ser-Ile-Pro-Pro-Ile-Cys(1)-Phe-Pro-Asp-Gly]；2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-25,34-bis[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid
• 化学式: C₆₇H₁₀₄N₂₀O₁₈S₂
• 分子量: 1541.82
• InChiKey: AMVNDXBEYOQKDS-MFPJKNJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  107
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  638
• 氢给体数：
  18
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  cyclo[Arg-Cys-Thr-Arg-Ser-Ile-Pro-Pro-Ile-Cys-Phe-Pro-Asp-Gly] 在 N-甲基吗啉 、 氧气 作用下， 以 水 为溶剂， 反应 24.0h， 生成 ¹Gly-Arg-Cys(²)-Thr-Arg-Ser-Ile-Pro-Pro-Ile-Cys(²)-Phe-Pro-Asp¹
  参考文献：
  名称：

  US2005/130883

  摘要：

  公开号：

文献信息

• Improving the Selectivity of Engineered Protease Inhibitors: Optimizing the P2 Prime Residue Using a Versatile Cyclic Peptide Library
  作者：Simon J. de Veer、Conan K. Wang、Jonathan M. Harris、David J. Craik、Joakim E. Swedberg

  DOI：10.1021/acs.jmedchem.5b01148

  日期：2015.10.22

  Standard mechanism inhibitors are attractive design templates for engineering reversible serine protease inhibitors. When optimizing interactions between the inhibitor and target protease, many studies focus on the nonprimed segment of the inhibitor's binding loop (encompassing the contact beta-strand). However, there are currently few methods for screening residues on the primed segment. Here, we designed a synthetic inhibitor library (based on sunflower trypsin inhibitorI) for characterizing the P2' specificity of various serine proteases. Screening the library against 13 different proteases revealed unique P2' preferences for trypsin, ch-ymotrypsin, matriptase, plasmin, thrombin, four kallikrein-related peptidases, and several clotting factors. Using this information to modify existing engineered inhibitors yielded new variants that showed considerably improved selectivity, reaching up to 7000-fold selectivity over certain off-target proteases. Our study demonstrates the importance of the P2' residue in standard mechanism inhibition and unveils a new approach for screening P2' substitutions that will benefit future inhibitor engineering studies.
• US2005/130883
  申请人：——

  公开号：——

  公开（公告）日：——