H-c[Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys]-OH

• 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: H-c[Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys]-OH
• 英文别名: cyclo(3-14)H-Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys-OH；H-Cys(1)-Phe-Phe-Trp-Lys-Thr-Phe-Cys(1)-OH；(4R,7S,10S,13S,16S,19S,22S,25R)-25-amino-13-(4-aminobutyl)-7,19,22-tribenzyl-10-[(1R)-1-hydroxyethyl]-16-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacosane-4-carboxylic acid
• 化学式: C₅₄H₆₆N₁₀O₁₀S₂
• 分子量: 1079.31
• InChiKey: PJRZZHKHLDKTKL-VJLATZRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  76
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  380
• 氢给体数：
  12
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  、 BOC-L-苯丙氨酸 、 N-Boc-O-苄基-L-苏氨酸 、 Boc-S-(4-甲氧基苄基)-L-半胱氨酸 、 N-叔丁氧羰基-N'-(2-氯苄氧羰基)-L-赖氨酸 、 N-叔丁氧羰基-L-色氨酸 在 间甲酚 、 三氟乙酸 、 N-甲基吡咯烷酮 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 反应 1.25h， 生成 H-c[Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys]-OH
  参考文献：
  名称：

  N-Imidazolebenzyl-histidine Substitution in Somatostatin and in Its Octapeptide Analogue Modulates Receptor Selectivity and Function

  摘要：

  Despite 3 decades of focused chemical, biological, structural, and clinical developments, unusual properties of somatostatin (SRIF, 1) analogues are still being uncovered. Here we report the unexpected functional properties of 1 and the octapeptide cyclo(3-14)H-Cys-Phe-Phe-Trp(8)-Lys-Thr-Phe-Cys-OH (somatostatin numbering; OLT-8,9) substituted by imBzl-L- or -D-His at position 8. These analogues were tested for their binding affinity to the five human somatostatin receptors (sst(1-5)), as well as for their functional properties (or functionalities) in an sst(3) internalization assay and in an sst(3) luciferase reporter gene assay. While substitution of Trp(8) in somatostatin by imBzl-L-or-D-His(8) results in sst(3) selectivity, substitution of Trp(8) in the octapeptide 9 by imBzl-L-or-D-His(8) results in loss of binding affinity for sst(1,2,4,5) and a radical functional switch from agonist to antagonist.

  DOI：

  10.1021/jm200307v

文献信息

• <i>N</i>-Imidazolebenzyl-histidine Substitution in Somatostatin and in Its Octapeptide Analogue Modulates Receptor Selectivity and Function
  作者：Judit Erchegyi、Renzo Cescato、Beatrice Waser、Jean E. Rivier、Jean Claude Reubi

  DOI：10.1021/jm200307v

  日期：2011.9.8

  Despite 3 decades of focused chemical, biological, structural, and clinical developments, unusual properties of somatostatin (SRIF, 1) analogues are still being uncovered. Here we report the unexpected functional properties of 1 and the octapeptide cyclo(3-14)H-Cys-Phe-Phe-Trp(8)-Lys-Thr-Phe-Cys-OH (somatostatin numbering; OLT-8,9) substituted by imBzl-L- or -D-His at position 8. These analogues were tested for their binding affinity to the five human somatostatin receptors (sst(1-5)), as well as for their functional properties (or functionalities) in an sst(3) internalization assay and in an sst(3) luciferase reporter gene assay. While substitution of Trp(8) in somatostatin by imBzl-L-or-D-His(8) results in sst(3) selectivity, substitution of Trp(8) in the octapeptide 9 by imBzl-L-or-D-His(8) results in loss of binding affinity for sst(1,2,4,5) and a radical functional switch from agonist to antagonist.