FMOC-N-甲基-D-正亮氨酸 | 1217482-47-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: FMOC-N-甲基-D-正亮氨酸
• 英文名称: N^αFmoc-D-MeNle-OH
• 英文别名: (R)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)hexanoic acid；(2R)-2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]hexanoic acid
• CAS: 1217482-47-7
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: RZZXDYZWHUAOEK-HXUWFJFHSA-N

物化性质

• 沸点：
  542.6±29.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  FMOC-N-甲基-D-正亮氨酸 、 Fmoc-甘氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-L-色氨酸(Boc)-OH 、 alkaline earth salt of/the/ methylsulfuric acid 生成 H-Tyr-Gly-Gly-Trp-N-methyl-L-norleucyl-Asp-Phe-NH2
  参考文献：
  名称：

  Structure−Activity Relationships of Bifunctional Peptides Based on Overlapping Pharmacophores at Opioid and Cholecystokinin Receptors

  摘要：

  Cholecystokinin (CCK) has been identified as a pronociceptive endogenous peptide which also possesses antiopioid actions. CCK may be upregulated in conditions of chronic pain or during sustained morphine administration resulting in attenuation of opioid-mediated pain relief. These complex interactions between opioids and endogenous CCK receptor systems have suggested the need for a new paradigm in drug design for some states of chronic pain. In these circumstances the rational design of potential drugs for the treatment of these conditions must be based on one ligand for multiple targets. We have designed a single peptide which can interact with delta and mu opioid receptors as agonists and with CCK receptors as antagonists. The ligands were designed based on a model of overlapping pharmacophores of opioid and CCK peptide ligands, which incorporates opioid pharmacophores at the N-terminal and CCK tetrapeptide pharmacophores at the C-terminal of the designed ligands. We measured binding and activities of our bifunctional peptides at opioid and CCK receptors. Compound 11 (Tyr-D-Ala-Gly-D-Trp-NMeNle-Asp-Phe-NH2) demonstrated opioid agonist properties at delta and mu receptors (IC50 = 63 +/- 27 nM and 150 +/- 65 nM, respectively in MVD and GPI tissue assays) and high binding affinity at CCK-1 and CCK-2 receptors (K-i = 320 and 1.5 nM, respectively). Compound 9 (Tyr-D-Nle-Gly-Trp-Nle-Asp-Phe-NH2) displayed potent agonist activity at delta and mu receptors (IC50 = 23 +/- 10 nM and 210 +/- 52 nM, respectively in MVD and GPI tissue assays), with a balanced binding affinity for CCK-1 and CCK-2 receptors (K-i = 9.6 and 15 nM, respectively). These results provide evidence supporting the concept that opioid and CCK receptors have overlapping pharmacophores required for binding affinity and biological activity and that designing overlapping pharmacophores of two peptides into a single peptide is a valid drug design approach.

  DOI：

  10.1021/jm050921q