2-[(1R,4S,7S,13S,16S,19S,24R,27S,30S,33S,40S)-40-[(2-aminoacetyl)amino]-24-carbamoyl-4,27-bis[3-(diaminomethylideneamino)propyl]-16-(hydroxymethyl)-30-(1H-indol-3-ylmethyl)-33-methyl-3,6,12,15,18,26,29,32,35,41-decaoxo-22,37-dithia-2,5,11,14,17,25,28,31,34,42-decazatricyclo[17.16.7.07,11]dotetracontan-13-yl]acetic acid | 1333332-14-1

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: 2-[(1R,4S,7S,13S,16S,19S,24R,27S,30S,33S,40S)-40-[(2-aminoacetyl)amino]-24-carbamoyl-4,27-bis[3-(diaminomethylideneamino)propyl]-16-(hydroxymethyl)-30-(1H-indol-3-ylmethyl)-33-methyl-3,6,12,15,18,26,29,32,35,41-decaoxo-22,37-dithia-2,5,11,14,17,25,28,31,34,42-decazatricyclo[17.16.7.07,11]dotetracontan-13-yl]acetic acid
• CAS: 1333332-14-1
• 化学式: C₅₄H₈₂N₂₀O₁₅S₂
• 分子量: 1315.5
• InChiKey: QZPBXLLGZXTMKA-NVTSEHFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -8.5
• 重原子数：
  91
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  633
• 氢给体数：
  19
• 氢受体数：
  20

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 FMOC-O-叔丁基二甲基硅基-L-高丝氨酸 、 在 三苯基二氯化膦 、 三丁基膦 作用下， 以 二氯甲烷 、 四氢呋喃 、 水 为溶剂， 反应 8.0h， 生成 2-[(1R,4S,7S,13S,16S,19S,24R,27S,30S,33S,40S)-40-[(2-aminoacetyl)amino]-24-carbamoyl-4,27-bis[3-(diaminomethylideneamino)propyl]-16-(hydroxymethyl)-30-(1H-indol-3-ylmethyl)-33-methyl-3,6,12,15,18,26,29,32,35,41-decaoxo-22,37-dithia-2,5,11,14,17,25,28,31,34,42-decazatricyclo[17.16.7.07,11]dotetracontan-13-yl]acetic acid
  参考文献：
  名称：

  α-Conotoxin ImI Incorporating Stable Cystathionine Bridges Maintains Full Potency and Identical Three-Dimensional Structure

  摘要：

  The two disulfide bonds of alpha-conotoxin ImI, a peptide antagonist of the alpha 7 nicotinic acetylcholine receptor (nAChR), were systematically replaced with isosteric redox-stable cystathionine thioethers. Regioselective thioether formation was accomplished on solid support through substitution of a gamma-chlorohomoalanine by an intramolecular cysteine thiol to produce hybrid thioether/disulfide analogues (2 and 3) as well as a dual cystathionine analogue (4) that were found to be structurally homologous to alpha-conotoxin ImI by (1)H NMR. The antagonistic activity at the alpha 7 nAChR of cystathionine analogue 3 (pIC(50) = 6.41 +/- 0.09) was identical to that of alpha-conotoxin ImI (1, pIC(50) = 6.41 +/- 0.09), whereas those of 2 (pIC(50) = 5.96 +/- 0.09) and 4 (pIC(50) = 5.89 +/- 0.09) showed a modest decrease. The effect of oxidation of the thioethers to sulfoxides was also investigated, with significant changes in the biological activities observed ranging from a >30-fold reduction (28=O) to a 3-fold increase (38=O(B)) in potencies.

  DOI：

  10.1021/ja206408q

文献信息

• α-Conotoxin ImI Incorporating Stable Cystathionine Bridges Maintains Full Potency and Identical Three-Dimensional Structure
  作者：Zoltan Dekan、Irina Vetter、Norelle L. Daly、David J. Craik、Richard J. Lewis、Paul F. Alewood

  DOI：10.1021/ja206408q

  日期：2011.10.12

  The two disulfide bonds of alpha-conotoxin ImI, a peptide antagonist of the alpha 7 nicotinic acetylcholine receptor (nAChR), were systematically replaced with isosteric redox-stable cystathionine thioethers. Regioselective thioether formation was accomplished on solid support through substitution of a gamma-chlorohomoalanine by an intramolecular cysteine thiol to produce hybrid thioether/disulfide analogues (2 and 3) as well as a dual cystathionine analogue (4) that were found to be structurally homologous to alpha-conotoxin ImI by (1)H NMR. The antagonistic activity at the alpha 7 nAChR of cystathionine analogue 3 (pIC(50) = 6.41 +/- 0.09) was identical to that of alpha-conotoxin ImI (1, pIC(50) = 6.41 +/- 0.09), whereas those of 2 (pIC(50) = 5.96 +/- 0.09) and 4 (pIC(50) = 5.89 +/- 0.09) showed a modest decrease. The effect of oxidation of the thioethers to sulfoxides was also investigated, with significant changes in the biological activities observed ranging from a >30-fold reduction (28=O) to a 3-fold increase (38=O(B)) in potencies.