Boc-Trp-Phe-NH2 | 33900-27-5

• 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: Boc-Trp-Phe-NH2
• 英文别名: Boc-Trp-PheNH2；Boc-WF-NH2；[1-(1-Carbamoyl-2-phenyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 33900-27-5
• 化学式: C₂₅H₃₀N₄O₄
• 分子量: 450.538
• InChiKey: BBVKWFPUAZBKNG-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-Trp-Phe-NH2 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 Trp-Phe-NH2
  参考文献：
  名称：

  使用有机物高效化学酶促合成Endomorphin-1 溶剂 稳定的蛋白酶可绿色合成肽

  摘要：

  内啡肽1（Tyr-Pro-Trp-Phe-NH 2，EM-1），有效 止痛药通过酶促方法和化学方法的有效合成。 肽类Boc-Trp-Phe-NH 2的合成产率高达97.1％。溶剂在20％甲醇培养基中的稳定蛋白酶WQ9-2。在经济的底物摩尔比为1 ：1的情况下，获得Boc-Trp-Phe-NH 2的最大浓度（141 g L -1）。纯化，然后通过以下方式删除Boc小组： 三氟乙酸 产生 色氨酸-苯丙氨酸-NH 2。使用高效混合碳酸酐 方法， Boc-Tyr-Pro-OH是化学合成的。通过另一种有机化合物合成了四肽Boc-Tyr-Pro-Trp-Phe-NH 2，收率为84.5％。溶剂耐蛋白酶，PT121，来自 Boc-Tyr-Pro-OH和Trp-Phe-NH 2在有机-水双相系统中，并用乙酸乙酯，移动合成的平衡。EM-1是通过从Boc-Tyr-Pro-Trp-Phe-NH 2中除去Boc基

  DOI：

  10.1039/c1gc15042a
• 作为产物：
  描述：

  (S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionamide 在 盐酸 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 Boc-Trp-Phe-NH2
  参考文献：
  名称：

  Endomorphin-1 analogs with enhanced metabolic stability and systemic analgesic activity: Design, synthesis, and pharmacological characterization

  摘要：

  We synthesized four new analogs of endomorphin-1 by systematic chemical modifications. To identify the best possible drug candidates for clinical pain management and to investigate the potential contribution of these alterations to the biological activity, their pharmacological properties were determined. All of the analogs showed significantly enhanced metabolic stability. The fact that centrally mediated analgesia following peripheral administration was observed with one of the analogs suggested the approach design undertaken here had validity in the development of endomorphin-1 as a successful opioid drug for the clinic. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.007

文献信息

• Stability against enzymatic hydrolysis of endomorphin-1 analogues containing β-proline
  作者：Giuliana Cardillo、Luca Gentilucci、Alessandra Tolomelli、Maria Calienni、Ahmed R. Qasem、Santi Spampinato

  DOI：10.1039/b301507f

  日期：2003.4.23

  The enantiomer of endomorphin-1 (Tyr-Pro-Trp-PheNH2) and the analogues containing (S)- or (R)-β-proline have been synthesized, and their affinities towards μ-opioid receptors have been measured. As expected, the incubations of the different peptides with some commercially available enzymes showed that the presence of D-residues gave strong resistance towards digestion. The presence of β-proline alone is sufficient to confer good resistance against the hydrolysis of the biologically strategic Pro–Trp bond.

  内啡肽-1（Tyr-Pro-Trp-PheNH2）的对映体及其含（S）-或（R）-β-脯氨酸的类似物已被合成，并测定了它们对μ-阿片受体的亲和力。如预期所料，不同肽与一些商业可用酶的共育显示，D-残基的存在赋予了较强的抵抗消化能力。β-脯氨酸单独的存在就足以赋予生物学上关键的Pro-Trp键良好的抵抗水解能力。
• Conformational analysis and μ-opioid receptor affinity of short peptides, endomorphin models in a low polarity solvent
  作者：Giuliana Cardillo、Luca Gentilucci、Alessandra Tolomelli、Ahmed R. Qasem、Santi Spampinato、Maria Calienni

  DOI：10.1039/b306161m

  日期：——

  Peptide carbamates containing the sequence H-Pro-Trp-PheNH2 showed in CDCl3 restricted conformations stabilized by the presence of a gamma-turn. To test the reliability of the peptides as endomorphin conformational models, we measured the affinities for mu-receptors labelled with [3H]-DAMGO. In particular, Cbz-Pro-Trp-PheNH2 displayed a nanomolar affinity.

  含有序列H-Pro-Trp-PheNH2的氨基甲酸酯肽在CDCl3限制的构象中显示，可通过存在伽马转角来稳定。为了测试作为内啡肽构象模型的肽的可靠性，我们测量了用[3H] -DAMGO标记的mu受体的亲和力。特别地，Cbz-Pro-Trp-PheNH2显示出纳摩尔亲和力。
• Endomorphin-1 Analogues Containing β-Proline Are μ-Opioid Receptor Agonists and Display Enhanced Enzymatic Hydrolysis Resistance
  作者：Giuliana Cardillo、Luca Gentilucci、Ahmed R. Qasem、Fabio Sgarzi、Santi Spampinato

  DOI：10.1021/jm011059z

  日期：2002.6.1

  In this paper we describe the synthesis and affinity toward the mu-opioid receptor of some tetrapeptides obtained from endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (1), by substituting each amino acid in turn with its homologue. The ability to bind p-opioid receptors depends on the beta-amino acid, and in particular 4, which contains beta-L-Pro, has a K-1 in the nanomolar range. The peptides 4 and 5 are significantly more resistant to enzymatic hydrolysis than 1. The same compounds, as well as they-opioid receptor agonist DAMGO, produced a concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation, thus behaving as mu-opioid agonists. These features suggest that this novel class of endomorphin-1 analogues may represent suitable candidates for the in vivo investigation as potential mu-opioid receptor agonists.
• Functional profiling of p53-binding sites in Hdm2 and Hdmx using a genetic selection system
  作者：Shreya Datta、Megan E. Bucks、Dipankar Koley、Pei Xin Lim、Sergey N. Savinov

  DOI：10.1016/j.bmc.2010.06.053

  日期：2010.8

  Upregulation of structurally homologous oncoproteins Hdm2 and Hdmx has been linked to the depletion or inactivation of their common regulation target the tumor suppressor p53 protein leading to the progression of cancer. The restoration of the p53 function, rendered suppressed or dormant by these negative regulators, establishes, therefore, a unique opportunity for a targeted induction of apoptosis in cancers that retain wild-type p53. While several small molecules have been reported to rescue the tumor suppressor by antagonizing the Hdm2-p53 interaction, these agents displayed limited application scope by being ineffective in tumors enriched with active Hdmx. Here, we describe the use of a genetic selection system and encoded library of conformationally pre-organized peptides to perform functional profiling of each regulator revealing specific recognition features that guide the antagonism of Hdm2-p53 and Hdmx-p53 interactions. Structure-activity relationship analysis of the most effective leads identified functional and structural elements mediating selective recognition of the two structurally related regulators, while providing convenient starting points for further activity optimization. (C) 2010 Elsevier Ltd. All rights reserved.
• Transformation of μ-opioid receptor agonists into biologically potent μ-opioid receptor antagonists
  作者：Tingyou Li、Yunden Jinsmaa、Masahiro Nedachi、Anna Miyazaki、Yuko Tsuda、Akihiro Ambo、Yusuke Sasaki、Sharon D. Bryant、Ewa Marczak、Qiang Li

  DOI：10.1016/j.bmc.2006.11.019

  日期：2007.2.1

  N-Allylation (-CH2-CH=CH2) of [Dmt(1)]endomorphins yielded the following: (i) [N-allyl-Dmt(1)]endomorphin-2 (Dmt = 2',6'-dimethyl-L-tyrosine) (12) and [N-allyl-Dmt(1)]endomorphin-1 (15) (K-i mu = 0.45 and 0.26 nM, respectively) became p-antagonists (pA(2) = 8.59 and 8.18, respectively) with weak delta-antagonism (pA(2) = 6.32 and 7.32, respectively); (ii) intracerebroventricularly administered 12 inhibited morphine-induced CNS-mediated antinociception in mice [AD(50) (0.148 ng/mouse) was 16-fold more potent than naloxone], but not spinal antinociception, and (iii) 15 reversed the alcohol-elevated frequency in spontaneous inhibitory post-synaptic currents (IPSC) in hippocampal CA1 pyramidal cells in rat brain slices (P = 0.0055). Similarly, N-allylation of the potent mu-opioidmimetic agonists, 1,6-bis-[H-Dmt-NH]-hexane and 3,6-bis-[Dmt-NH-propyl]-2(1H)-pyrazinone, converted them into p-antagonists (pA(2) = 7.23 and 7.17 for the N-allyl-derivatives 17 and 19, respectively), and exhibited weak delta-antagonism. Thus, N-allylation of Dmt containing opioid peptides or opioidmimetics; continues to provide a facile means to convert selective mu-opioid agonists into potent mu-opioid antagonists. (c) 2006 Elsevier Ltd. All rights reserved.