Fmoc-Orn(Me)2-OH | 949572-12-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Orn(Me)2-OH
• 英文别名: (2S)-5-(dimethylamino)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoic acid
• CAS: 949572-12-7
• 化学式: C₂₂H₂₆N₂O₄
• 分子量: 382.459
• InChiKey: BSEMVUINIVEPDK-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  28.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.87
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Fmoc-Orn(Me)2-OH 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以150 mg的产率得到(2S)-5-(dimethylamino)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)pentanoic acid hydrochloride
  参考文献：
  名称：

  JmjC 加氧酶催化是否仅限于去甲基化？

  摘要：

  上侧的作业：底物选择性的研究表明，生物医学重要JmjC结构的成员家族脱甲基酶的组蛋白的Ñ ε -methyllysine脱甲基酶是能够催化去的Ñ比其它基团的烷基化ñ -甲基和可催化反应，其形成稳定的羟基化产品。这组酶中结合偏好的差异可能有助于设计选择性抑制剂。

  DOI：

  10.1002/anie.201303282
• 作为产物：
  描述：

  在 三乙基硅烷 、 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 8.0h， 生成 Fmoc-Orn(Me)2-OH
  参考文献：
  名称：

  Facile synthesis of mono- and bis-methylated Fmoc-Dap, -Dab and -Orn amino acids

  摘要：

  一种简便的单甲基化和双甲基化Fmoc-Dap、-Dab和-Orn氨基酸的选择性合成方法，可在一个反应体系中完成。

  DOI：

  10.1039/c4cc09780g

文献信息

• Recognition of shorter and longer trimethyllysine analogues by epigenetic reader proteins
  作者：Abbas H. K. Al Temimi、Roman Belle、Kiran Kumar、Jordi Poater、Peter Betlem、Bas J. G. E. Pieters、Robert S. Paton、F. Matthias Bickelhaupt、Jasmin Mecinović

  DOI：10.1039/c8cc01009a

  日期：——

  Combined thermodynamic data, molecular dynamics simulations, and quantum chemical studies reveal that epigenetic reader proteins efficiently bind trimethylornithine and trimethylhomolysine.

  结合热力学数据、分子动力学模拟和量子化学研究揭示了表观遗传读取蛋白高效地结合了三甲基鸟氨酸和三甲基同赖氨酸。
• Effects of Chain Length and N-Methylation on a Cation–π Interaction in a β-Hairpin Peptide
  作者：Robert M. Hughes、Matthew L. Benshoff、Marcey L. Waters

  DOI：10.1002/chem.200601753

  日期：2007.7.6

  The effects of N-methylation and chain length on a cation-pi interaction have been investigated within the context of a beta-hairpin peptide. Significant enhancement of the interaction and structural stabilization of the hairpin have been observed upon Lys methylation. Thermodynamic analysis indicates an increased entropic driving force for folding upon methylation of Lys residues. Comparison of lysine

  在β-发夹肽的背景下，已经研究了N-甲基化和链长对阳离子-pi相互作用的影响。Lys甲基化后已观察到发夹相互作用和结构稳定的显着增强。热力学分析表明，当赖氨酸残基甲基化时，折叠时的熵驱动力增加。赖氨酸与类似物鸟氨酸（Orn）和二氨基丁酸（Dab）的比较表明，由于侧链-侧链相互作用和β-折叠倾向的结合，赖氨酸提供最强的阳离子-pi相互作用，还提供最稳定的β-发夹结构。这些研究对于识别组蛋白中的甲基化赖氨酸具有重要意义。
• Strategy for “Detoxification” of a Cancer-Derived Histone Mutant Based on Mapping Its Interaction with the Methyltransferase PRC2
  作者：Zachary Z. Brown、Manuel M. Müller、Siddhant U. Jain、C. David Allis、Peter W. Lewis、Tom W. Muir

  DOI：10.1021/ja5060934

  日期：2014.10.1

  The histone methyltransferase PRC2 plays a central role in genomic stability and cellular development. Consequently, its misregulation has been implicated in several cancers. Recent work has shown that a histone H3 mutant, where the PRC2 substrate residue Lys27 is replaced by methionine, is also associated with cancer phenotypes and functions as an inhibitor of PRC2. Here we investigate the mechanism of this PRC2 inhibition through kinetic studies and photo-cross-linking. Efficient inhibition is dependent on (1) hydrophobic lysine isosteres blocking the active site, (2) proximal residues, and (3) the H3 tail forming extensive contacts with the EZH2 subunit of PRC2. We further show that naturally occurring post-translational modifications of the same H3 tail, both proximal and distal to K27M, can greatly diminish the inhibition of PRC2. These results suggest that this potent gain of function mutation may be detoxified by modulating alternate chromatin modification pathways.
• Iterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity
  作者：Padmavathy Nandha Premnath、Sandra N. Craig、Shu Liu、Erin L. Anderson、Asterios I. Grigoroudis、George Kontopidis、Tracy L. Perkins、Michael D. Wyatt、Douglas L. Pittman、Campbell McInnes

  DOI：10.1021/jm5015023

  日期：2015.1.8

  The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structureactivity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of proteinprotein interactions into pharmaceutically relevant compounds. As a result, REPLACE is further exemplified in combining optimized peptidic sequences with effective N-terminal capping groups to generate more stable compounds possessing antitumor activity consistent with on-target inhibition of cell cycle CDKs. The compounds described here represent prototypes for a next generation of kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with first generation CDK inhibitors.