cyclo(3-14)H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-3-(2-naphthyl)alanine-Lys-Thr-Phe-Thr-Ser-Cys-OH | 66863-48-7

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: cyclo(3-14)H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-3-(2-naphthyl)alanine-Lys-Thr-Phe-Thr-Ser-Cys-OH
• 英文别名: H-Ala-Gly-Cys(1)-Lys-Asn-Phe-Phe-2Nal-Lys-Thr-Phe-Thr-Ser-Cys(1)-OH；(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,34S,37R)-19,34-bis(4-aminobutyl)-31-(2-amino-2-oxoethyl)-37-[[2-[[(2S)-2-aminopropanoyl]amino]acetyl]amino]-13,25,28-tribenzyl-10,16-bis[(1R)-1-hydroxyethyl]-7-(hydroxymethyl)-22-(naphthalen-2-ylmethyl)-6,9,12,15,18,21,24,27,30,33,36-undecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35-undecazacyclooctatriacontane-4-carboxylic acid
• CAS: 66863-48-7
• 化学式: C₇₈H₁₀₅N₁₇O₁₉S₂
• 分子量: 1648.93
• InChiKey: PPMRXEMNCQTEFU-DQMVLKBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  116
• 可旋转键数：
  26
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  648
• 氢给体数：
  21
• 氢受体数：
  24

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 N-叔丁氧羰基-L-丙氨酸 、 、 BOC-L-苯丙氨酸 、 N-Boc-O-苄基-L-苏氨酸 、 N-BOC-O-苄基-L-丝氨酸 、 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 、 Boc-3-(2-萘基)-L-丙氨酸 、 N-叔丁氧羰基-N'-氧蒽基-L-天门冬酰胺 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 cyclo(3-14)H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-3-(2-naphthyl)alanine-Lys-Thr-Phe-Thr-Ser-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.