Gly-Phe-Phe-NH2 | 34367-79-8

• 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: Gly-Phe-Phe-NH2
• 英文别名: GFF-NH₂；Glycyl-L-phenylalanyl-L-phenylalaninamide；(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-phenylpropanoyl]amino]-3-phenylpropanamide
• CAS: 34367-79-8
• 化学式: C₂₀H₂₄N₄O₃
• 分子量: 368.436
• InChiKey: FGCIXAIKBNQNPD-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  127
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Gly-Phe-Phe-NH2 、 2-[2-((S)-2,6-Bis-tert-butoxycarbonylamino-hexanoylamino)-acetylamino]-3-phenyl-propionic acid 3-formyl-2-(2,4,6-trimethoxy-benzylsulfanyl)-phenyl ester 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以77%的产率得到2-[2-((S)-2,6-Bis-tert-butoxycarbonylamino-hexanoylamino)-acetylamino]-3-phenyl-propionic acid 3-[({[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-2-phenyl-ethylcarbamoyl]-methyl}-amino)-methyl]-2-(2,4,6-trimethoxy-benzylsulfanyl)-phenyl ester
  参考文献：
  名称：

  Studies Related to the Relative Thermodynamic Stability of C-Terminal Peptidyl Esters of O-Hydroxy Thiophenol:  Emergence of a Doable Strategy for Non-Cysteine Ligation Applicable to the Chemical Synthesis of Glycopeptides

  摘要：

  A pathway has been devised, wherein a phenolic ester of a C-terminal peptide is ligated with an N-terminal peptide through two consecutive acyl migrations. In the first transacylation, the C-terminus is transferred from a phenol to a newly liberated ortho-thiol function. Subsequently, the acyl group is transported to a proximal benzylamine through a six-membered transition state.

  DOI：

  10.1021/ja061588y
• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-苯丙氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 Gly-Phe-Phe-NH2
  参考文献：
  名称：

  Molecular and Physiological Characterization of a Receptor for d-Amino Acid-Containing Neuropeptides

  摘要：

  Neuropeptides in several animals undergo an unusual post-translational modification, the isomerization of an amino acid residue from the L-stereoisomer to the D-stereoisomer. The resulting D-amino acid-containing peptide (DAACP) often displays biological activity higher than that of its all-L-residue analogue, with the D-residue being critical for function in many cases. However, little is known about the full physiological roles played by DAACPs, and few studies have examined the interaction of DAACPs with their cognate receptors. Here, we characterized the signaling of several DAACPs derived from a single neuropeptide prohormone, the Aplysia californica achatin-like neuropeptide precursor (apALNP), at their putative receptor, the achatin-like neuropeptide receptor (apALNR). We first used quantitative polymerase chain reaction and in situ hybridization experiments to demonstrate receptor (apALNR) expression throughout the central nervous system; on the basis of the expression pattern, we identified novel physiological functions that may be mediated by apALNR. To gain insight into ligand signaling through apALNR, we created a library of native and non-native neuropeptide analogues derived from apALNP (the neuropeptide prohormone) and evaluated them for activity in cells co-transfected with apALNR and the promiscuous G alpha subunit G alpha-16. Several of these neuropeptide analogues were also evaluated for their ability to induce circuit activity in a well-defined neural network associated with feeding behavior in intact ganglia from Aplysia. Our results reveal the specificity of apALNR and provide strong evidence that this receptor mediates diverse physiological functions throughout the central nervous system. Finally, we show that some native apALNP-derived DAACPs exhibit enhanced stability toward endogenous proteases, suggesting that the D-residues in these DAACPs may increase the peptide lifetime, in addition to influencing receptor specificity, in the nervous system. Ultimately, these studies provide insight into signaling at one of the few known DAACP-specific receptors and advance our understanding of the roles that L- to D-residue isomerization play in neuropeptide signaling.

  DOI：

  10.1021/acschembio.8b00167

文献信息

• Studies Related to the Relative Thermodynamic Stability of C-Terminal Peptidyl Esters of O-Hydroxy Thiophenol:  Emergence of a Doable Strategy for Non-Cysteine Ligation Applicable to the Chemical Synthesis of Glycopeptides
  作者：Gong Chen、J. David Warren、Jiehao Chen、Bin Wu、Qian Wan、Samuel J. Danishefsky

  DOI：10.1021/ja061588y

  日期：2006.6.1

  A pathway has been devised, wherein a phenolic ester of a C-terminal peptide is ligated with an N-terminal peptide through two consecutive acyl migrations. In the first transacylation, the C-terminus is transferred from a phenol to a newly liberated ortho-thiol function. Subsequently, the acyl group is transported to a proximal benzylamine through a six-membered transition state.
• Molecular and Physiological Characterization of a Receptor for <scp>d</scp>-Amino Acid-Containing Neuropeptides
  作者：James W. Checco、Guo Zhang、Wang-ding Yuan、Ke Yu、Si-yuan Yin、Rachel H. Roberts-Galbraith、Peter M. Yau、Elena V. Romanova、Jian Jing、Jonathan V. Sweedler

  DOI：10.1021/acschembio.8b00167

  日期：2018.5.18

  Neuropeptides in several animals undergo an unusual post-translational modification, the isomerization of an amino acid residue from the L-stereoisomer to the D-stereoisomer. The resulting D-amino acid-containing peptide (DAACP) often displays biological activity higher than that of its all-L-residue analogue, with the D-residue being critical for function in many cases. However, little is known about the full physiological roles played by DAACPs, and few studies have examined the interaction of DAACPs with their cognate receptors. Here, we characterized the signaling of several DAACPs derived from a single neuropeptide prohormone, the Aplysia californica achatin-like neuropeptide precursor (apALNP), at their putative receptor, the achatin-like neuropeptide receptor (apALNR). We first used quantitative polymerase chain reaction and in situ hybridization experiments to demonstrate receptor (apALNR) expression throughout the central nervous system; on the basis of the expression pattern, we identified novel physiological functions that may be mediated by apALNR. To gain insight into ligand signaling through apALNR, we created a library of native and non-native neuropeptide analogues derived from apALNP (the neuropeptide prohormone) and evaluated them for activity in cells co-transfected with apALNR and the promiscuous G alpha subunit G alpha-16. Several of these neuropeptide analogues were also evaluated for their ability to induce circuit activity in a well-defined neural network associated with feeding behavior in intact ganglia from Aplysia. Our results reveal the specificity of apALNR and provide strong evidence that this receptor mediates diverse physiological functions throughout the central nervous system. Finally, we show that some native apALNP-derived DAACPs exhibit enhanced stability toward endogenous proteases, suggesting that the D-residues in these DAACPs may increase the peptide lifetime, in addition to influencing receptor specificity, in the nervous system. Ultimately, these studies provide insight into signaling at one of the few known DAACP-specific receptors and advance our understanding of the roles that L- to D-residue isomerization play in neuropeptide signaling.