(des-NH2)Tyr(SO3^-)-Nle-Gly-Trp-Nle-Asp-Phe-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: (des-NH2)Tyr(SO3^-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2
• 英文别名: [4-[3-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-oxopropyl]phenyl] sulfate
• 化学式: C₄₇H₅₉N₈O₁₃S
• 分子量: 976.097
• InChiKey: WLTSODCLBUFUDX-MQDBWYGVSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  69.0
• 可旋转键数：
  29.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  337.21
• 氢给体数：
  9.0
• 氢受体数：
  12.0

反应信息

• 作为产物：
  描述：

  对羟基苯丙酸 在 palladium on activated charcoal N-甲基吗啉 、 吡啶 、 三氧化硫 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、405.3 kPa 条件下， 反应 120.2h， 生成 (des-NH2)Tyr(SO3^-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2
  参考文献：
  名称：

  Synthesis and biological activity of CCK heptapeptide analogs. Effects of conformational constraints and standard modifications on receptor subtype selectivity, functional activity in vitro, and appetite suppression in vivo

  摘要：

  A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally restricted residues in the C-terminal tetrapeptide region, including DELTA(Z)-Phe33, (N-Me)Phe33, (N-Me)Asp32, (N-Me)Leu31, and 3PP31 (3PP = trans-3-n-propyl-L-proline) were found to be acceptable modifications at one or both receptor subtypes. The (N-Me)Asp32 and (N-Me)Leu31 modifications afforded potent and selective CCK-A and CCK-B ligands, respectively. SAR studies in the N-terminal acyldipeptide region examined structural requirements for the side chain at position 28, where Gly and Pro replacements were found to possess high affinity at both receptor subtypes. Other conformationally restrictive modifications were less active. All of the analogues that showed high affinity (<10 nM) for the CCK-A receptor also were full agonists in amylase release and most were full or nearly full agonists in the phosphoinositide (PI) turnover assay, the most notable exception being the DELTA(Z)-Phe33 analogue, which showed 69% of the maximal response in the PI assay. Potent activity in suppression of food intake in rats was found for selected analogues.

  DOI：

  10.1021/jm00094a001

文献信息

• Synthesis and biological activity of CCK heptapeptide analogs. Effects of conformational constraints and standard modifications on receptor subtype selectivity, functional activity in vitro, and appetite suppression in vivo
  作者：Mark W. Holladay、Michael J. Bennett、Michael D. Tufano、C. W. Lin、Karen E. Asin、David G. Witte、Thomas R. Miller、Bruce R. Bianchi、A. L. Nikkel

  DOI：10.1021/jm00094a001

  日期：1992.8

  A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally restricted residues in the C-terminal tetrapeptide region, including DELTA(Z)-Phe33, (N-Me)Phe33, (N-Me)Asp32, (N-Me)Leu31, and 3PP31 (3PP = trans-3-n-propyl-L-proline) were found to be acceptable modifications at one or both receptor subtypes. The (N-Me)Asp32 and (N-Me)Leu31 modifications afforded potent and selective CCK-A and CCK-B ligands, respectively. SAR studies in the N-terminal acyldipeptide region examined structural requirements for the side chain at position 28, where Gly and Pro replacements were found to possess high affinity at both receptor subtypes. Other conformationally restrictive modifications were less active. All of the analogues that showed high affinity (<10 nM) for the CCK-A receptor also were full agonists in amylase release and most were full or nearly full agonists in the phosphoinositide (PI) turnover assay, the most notable exception being the DELTA(Z)-Phe33 analogue, which showed 69% of the maximal response in the PI assay. Potent activity in suppression of food intake in rats was found for selected analogues.