(S)-N-Fmoc-2-(3’-丁烯)丙氨酸 | 288617-72-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (S)-N-Fmoc-2-(3’-丁烯)丙氨酸
• 中文别名: (S)-N-Fmoc-2-(3'-丁烯基)丙氨酸；N-芴甲氧羰基-2-(3'-丁烯基)-L-丙氨酸；(S)-N-芴甲氧羰基-2-(3'-丁烯基)-L-丙氨酸
• 英文名称: (S)-N-(9-fluorenylmethyl carbamate)-2-(2'-butenyl)alanine
• 英文别名: (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methylbut-5-enoic acid；Fmoc-(S)-2-(4-butenyl)alanine；N-Fmoc-(S)-α-methyl-α-butenylglycine；(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-2-methylhex-5-enoic acid；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-methylhex-5-enoic acid
• CAS: 288617-72-1
• 化学式: C₂₂H₂₃NO₄
• 分子量: 365.429
• InChiKey: ZZWOKVRONYEEBJ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (S)-N-Fmoc-2-(3’-丁烯)丙氨酸 、 (2R)-2-N-芴甲氧羰基氨基-2-甲基-6-庚烯酸 在 Grubbs catalyst first generation 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.2h， 生成
  参考文献：
  名称：

  水中五环肽的相对α-螺旋度

  摘要：

  螺旋限制的多肽引起了人们对调节蛋白质间相互作用（PPI）的极大兴趣。尚不清楚哪种是设计PPI激动剂/拮抗剂的最有效的螺旋诱导策略。使用圆二色性和2D NMR光谱比较了环化接头（X 1 –X 5）在简单模型五肽Ac‐cyclo（1,5）‐ [X 1 ‐Ala‐Ala‐Ala‐ X 5 ] -NH 2，在水中。在这个非常严格的螺旋诱导测试中，Lys1→Asp5内酰胺连接子具有最大的α-螺旋性，烃和三唑连接子诱导了α-和3 10的混合-螺旋性，而硫代和二硫醚连接子产生的螺旋度较小。内酰胺连接的环状五肽也是与13个残基模型肽连接的最有效的α螺旋成核剂。

  DOI：

  10.1002/anie.201310245
• 作为产物：
  描述：

  在 盐酸 、 乙二胺四乙酸 、 水 、 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.0h， 生成 (S)-N-Fmoc-2-(3’-丁烯)丙氨酸
  参考文献：
  名称：

  Influence of α-methylation in constructing stapled peptides with olefin metathesis

  摘要：

  Ring-closing metathesis is commonly utilized in peptide macro-cyclization. The influence of alpha-methylation of the amino acids bearing the olefin moieties has never been systematically studied. In this report, controlled reactions unambiguously indicate that alpha-methylation at the N-terminus of the metathesis sites is crucial for this reaction to occur. Also, we first elucidated that the E-isomers of stapled peptides are significantly more helical than the Z-isomers. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.08.004

文献信息

• Constrained Peptides with Target-Adapted Cross-Links as Inhibitors of a Pathogenic Protein-Protein Interaction
  作者：Adrian Glas、David Bier、Gernot Hahne、Christoph Rademacher、Christian Ottmann、Tom N. Grossmann

  DOI：10.1002/anie.201310082

  日期：2014.2.24

  Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic peptides proved useful as modulators of biological functions, in particular as inhibitors of protein–protein interactions (PPI). However, most peptide‐derived PPI inhibitors involve stabilized α‐helices, leaving a large number of secondary structures unaddressed

  肽的生物活性构象可以通过大环化来稳定，从而提高靶标亲和力和活性。这种大环肽被证明可作为生物学功能的调节剂，特别是作为蛋白-蛋白相互作用（PPI）的抑制剂。但是，大多数肽衍生的PPI抑制剂都涉及稳定的α螺旋，从而使大量二级结构无法解决。在本文中，我们提出了一种合理的方法来稳定不规则的肽结构，使用疏水性交联取代了关键地参与靶标结合的残基。X射线晶体学和等温滴定量热法阐明了这种相互作用的分子基础。产生的交联肽抑制了人类衔接蛋白14-3-3和毒力因子外切酶S之间的相互作用。
• Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors
  作者：Ya-Qiu Long、Shao-Xu Huang、Zahrah Zawahir、Zhong-Liang Xu、Huiyuan Li、Tino W. Sanchez、Ying Zhi、Stephanie De Houwer、Frauke Christ、Zeger Debyser、Nouri Neamati

  DOI：10.1021/jm4006516

  日期：2013.7.11

  HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the a-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their., helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead IN inhibitors but also prototypical biochemical probes or "nanoneedles" for the elucidation of HIV-1 IN dimerization and host cofactor interactions within their native cellular environment.
• An All-Hydrocarbon Cross-Linking System for Enhancing the Helicity and Metabolic Stability of Peptides
  作者：Christian E. Schafmeister、Julia Po、Gregory L. Verdine

  DOI：10.1021/ja000563a

  日期：2000.6.1
• Helix stabilization by stapled N-capping box
  作者：Thanh K. Pham、Young-Woo Kim

  DOI：10.1016/j.bioorg.2020.104024

  日期：2020.8

  The N-capping box is a distinct helix-stabilizing motif frequently found in proteins. In this study, we examined a ruthenium-mediated intramolecular backbone to side chain macrocyclization as a rigidified mimicry of the N-capping box. Experimental data indicate that the 15-membered macrocycle formed by a hept-4-enoyl staple, which directly tethers the alpha-amino group of N1 residue and the alpha-carbon of N3 residue, is highly effective in stabilizing helical structures of short peptides.
• Influence of α-methylation in constructing stapled peptides with olefin metathesis
  作者：Qingzhou Zhang、Xiaodong Shi、Yanhong Jiang、Zigang Li

  DOI：10.1016/j.tet.2014.08.004

  日期：2014.10

  Ring-closing metathesis is commonly utilized in peptide macro-cyclization. The influence of alpha-methylation of the amino acids bearing the olefin moieties has never been systematically studied. In this report, controlled reactions unambiguously indicate that alpha-methylation at the N-terminus of the metathesis sites is crucial for this reaction to occur. Also, we first elucidated that the E-isomers of stapled peptides are significantly more helical than the Z-isomers. (C) 2014 Elsevier Ltd. All rights reserved.