Gln-Ala-Phe-Ser-Arg | 1355048-51-9

• 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: Gln-Ala-Phe-Ser-Arg
• 英文别名: [Ala]2-opiorphin；H-Gln-Ala-Phe-Ser-Arg-OH；(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2,5-diamino-5-oxopentanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]pentanoic acid
• CAS: 1355048-51-9
• 化学式: C₂₆H₄₁N₉O₈
• 分子量: 607.667
• InChiKey: HWWYNFRGRWVCLR-GBBGEASQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  43
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  307
• 氢给体数：
  10
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  Fmoc-Arg(Pmc)-WANG resin 、 Fmoc-L-丙氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-N-三苯甲基-L-谷氨酰胺 、 Fmoc-O-叔丁基-D-丝氨酸 在 哌啶 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Gln-Ala-Phe-Ser-Arg
  参考文献：
  名称：

  Structure–Activity Relationship Study of Opiorphin, a Human Dual Ectopeptidase Inhibitor with Antinociceptive Properties

  摘要：

  Toward developing new potential analgesics, this first structure activity relationship study of opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH), a human peptide inhibiting enkephalin degradation, was performed. A systematic Ala scanning proved that Phe(3) is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalinase inhibition. A series of Phe(3)-halogenated analogues revealed that halogen bonding based optimization strategies are not applicable to this residue. Additional substituted Phe(3) derivatives showed that replacing L-Phe(3) for D-Phe(3) increased the AP-N inhibition potency by 1 order of magnitude. NMR studies and molecular mechanics calculations indicated that the improved potency may be due to CH-pi stacking interactions between the aromatic ring of D-Phe(3) and the H gamma protons of Arg(2). This structural motif is not possible for the native opiorphin and may be useful for the design of further potent and metabolically stable analogues.

  DOI：

  10.1021/jm2012112

文献信息

• Structure–Activity Relationship Study of Opiorphin, a Human Dual Ectopeptidase Inhibitor with Antinociceptive Properties
  作者：Mònica Rosa、Gemma Arsequell、Catherine Rougeot、Luis P. Calle、Filipa Marcelo、Marta Pinto、Nuria B. Centeno、Jesús Jiménez-Barbero、Gregorio Valencia

  DOI：10.1021/jm2012112

  日期：2012.2.9

  Toward developing new potential analgesics, this first structure activity relationship study of opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH), a human peptide inhibiting enkephalin degradation, was performed. A systematic Ala scanning proved that Phe(3) is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalinase inhibition. A series of Phe(3)-halogenated analogues revealed that halogen bonding based optimization strategies are not applicable to this residue. Additional substituted Phe(3) derivatives showed that replacing L-Phe(3) for D-Phe(3) increased the AP-N inhibition potency by 1 order of magnitude. NMR studies and molecular mechanics calculations indicated that the improved potency may be due to CH-pi stacking interactions between the aromatic ring of D-Phe(3) and the H gamma protons of Arg(2). This structural motif is not possible for the native opiorphin and may be useful for the design of further potent and metabolically stable analogues.