Fmoc-alpha-methyl-D-phenylalanine

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-alpha-methyl-D-phenylalanine
• 英文别名: (2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-methyl-3-phenylpropanoic acid
• 化学式: C₂₅H₂₃NO₄
• 分子量: 401.462
• InChiKey: KLBKBAAOPOXFSK-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-丝氨酸 、 Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 9H-fluoren-9-ylmethyl N-[(3S)-7-amino-2-oxoheptan-3-yl]carbamate 、 Fmoc-alpha-methyl-D-phenylalanine 、 Fmoc-L-脯氨酸 、 FMOC-L-精氨酸 、 芴甲氧羰酰基正亮氨酸 、 (2S)-1-(9H-芴-9-基甲氧羰基)-5-氧代吡咯烷-2-羧酸 、 N-芴甲氧羰基-L-组氨酸 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 哌啶 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 PyrRPRLSHKGPNleP(D-α-Me)Phe
  参考文献：
  名称：

  C-Terminal Modifications of Apelin-13 Significantly Change Ligand Binding, Receptor Signaling, and Hypotensive Action

  摘要：

  Apelin is the endogenous ligand of the APJ receptor, a member of the G protein-coupled receptor family. This system plays an important role in the regulation of blood pressure and cardiovascular functions. To better understand the role of its C-terminal Phe13 residue on ligand binding, receptor signaling, and hypotension, we report a series of modified analogues in which Phe13 was substituted by unnatural amino acids. These modifications delivered new compounds exhibiting higher affinity and potency to inhibit cAMP accumulation compared to apelin-13. In particular, analogues Bpa(13) or (alpha-Me)Phe(13) were 30-fold more potent to inhibit cAMP accumulation than apelin-13. Tyr(OBn)(13) substitution led to a 60-fold improvement in binding affinity and induced stronger and more sustained drop in blood pressure compared to apelin-13. Our study identified new potent analogues of apelin-13, which represent valuable probes to better understand its structurefunction relationship.

  DOI：

  10.1021/jm501916k

文献信息

• C-Terminal Modifications of Apelin-13 Significantly Change Ligand Binding, Receptor Signaling, and Hypotensive Action
  作者：Alexandre Murza、Élie Besserer-Offroy、Jérôme Côté、Patrick Bérubé、Jean-Michel Longpré、Robert Dumaine、Olivier Lesur、Mannix Auger-Messier、Richard Leduc、Philippe Sarret、Éric Marsault

  DOI：10.1021/jm501916k

  日期：2015.3.12

  Apelin is the endogenous ligand of the APJ receptor, a member of the G protein-coupled receptor family. This system plays an important role in the regulation of blood pressure and cardiovascular functions. To better understand the role of its C-terminal Phe13 residue on ligand binding, receptor signaling, and hypotension, we report a series of modified analogues in which Phe13 was substituted by unnatural amino acids. These modifications delivered new compounds exhibiting higher affinity and potency to inhibit cAMP accumulation compared to apelin-13. In particular, analogues Bpa(13) or (alpha-Me)Phe(13) were 30-fold more potent to inhibit cAMP accumulation than apelin-13. Tyr(OBn)(13) substitution led to a 60-fold improvement in binding affinity and induced stronger and more sustained drop in blood pressure compared to apelin-13. Our study identified new potent analogues of apelin-13, which represent valuable probes to better understand its structurefunction relationship.