H-Dip-cyclo(DCys-His-DTrp-Lys-Val-Cys)-Nal-NH2

• 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-Dip-cyclo(DCys-His-DTrp-Lys-Val-Cys)-Nal-NH2
• 英文别名: H-Dip-D-Cys(1)-His-D-Trp-Lys-Val-Cys(1)-2Nal-NH2；(4R,7S,10S,13R,16S,19S)-10-(4-aminobutyl)-19-[[(2S)-2-amino-3,3-diphenylpropanoyl]amino]-N-[(2S)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]-16-(1H-imidazol-5-ylmethyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
• 化学式: C₆₂H₇₃N₁₃O₈S₂
• 分子量: 1192.48
• InChiKey: BBRISWZNYQIAOC-QNBROOFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  85
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  394
• 氢给体数：
  12
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-N'-(2-氯苄氧羰基)-L-赖氨酸 、 N-Boc-3,3-二苯基-L-丙氨酸 、 、 Boc-Cys(4-Me-Z)-OH 、 alkaline earth salt of/the/ methylsulfuric acid 生成 H-Dip-cyclo(DCys-His-DTrp-Lys-Val-Cys)-Nal-NH2
  参考文献：
  名称：

  Potent Antagonists of Somatostatin:  Synthesis and Biology

  摘要：

  The search for synthetic analogues of somatostatin (SRIF) which exhibit selective affinities for the five known receptor subtypes (sst(1-5)) has generated a large number of potent agonist analogues. Many of these agonists display good subtype selectivities and affinities for the subtypes 2, 3, and 5, with very few selective for sst(1) or sst(4). Until the recent report by Bass and co-workers (Mel. Pharmacol. 1996, 50, 709-715; erratum, Mol. Pharmacol. 1997, 51, 170), no true antagonists had been discovered, let alone any displaying differential receptor subtype selectivity. In this present study, we explore the effect of this putative L-5,D-6 antagonist motif on various series of somatostatin agonist analogues, both linear and cyclic. It was found that many D-5,L-6 agonists could be converted into competitive antagonists by applying this motif, the most potent of which was H-Nal-cyclo[DCys-Pal-DTrp-Lys-Val-Cys]-Nal-NH2 (32). This antagonist was selective for hsst(2) with an affinity of 75 nM and an IC50 of 15.1 nM against SRIF-14 in a rat in vitro antagonist bioassay. Receptor-selective somatostatin antagonists should provide valuable tools for characterizing the many important physiological functions of this neuropeptide.

  DOI：

  10.1021/jm970730q