Fmoc-O-乙酰基-L-酪氨酸 | 918329-78-9

• 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
• 中文名称: Fmoc-O-乙酰基-L-酪氨酸
• 英文名称: Fmoc-Tyr(Ac)-OH
• 英文别名: O-Acetyl-N-{[(9H-fluoren-9-yl)methoxy]carbonyl}-L-tyrosine；(2S)-3-(4-acetyloxyphenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 918329-78-9
• 化学式: C₂₆H₂₃NO₆
• 分子量: 445.472
• InChiKey: DGYAMPGGERPSOR-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  Fmoc-L-酪氨酸	N-Fmoc-Tyr-OH	92954-90-0	C24H21NO5	403.434

反应信息

• 作为反应物：
  描述：

  Fmoc-O-乙酰基-L-酪氨酸 、 溴甲苯 生成 (S)-2-benzylamino-N-hydroxy-3-(4-hydroxyphenyl)propanamide
  参考文献：
  名称：

  Design and Evaluation of Hydroxamate Derivatives as Metal-Mediated Inhibitors of a Protein Tyrosine Kinase

  摘要：

  Protein tyrosine kinases use two Mg2+ ions as cofactors in catalysis, one as the ATP-Mg complex (M1) and the other as an essential activator (M2). The M2-binding site has high affinity for transition metal cations such as cobalt and zinc. Taking advantage of this high affinity, we examined hydroxamates as metal-mediated inhibitors against C-terminal Src kinase (Csk), a protein tyrosine kinase. Of a small group of amino acid hydroxamates, tyrosine and phenylalanine hydroxamates inhibited Csk activity only in the presence of Co2+. Four classes of phenylalanine and tyrosine hydroxamate derivatives were synthesized and evaluated as metal-mediated inhibitors of Csk, leading to improved inhibition and a better understanding of the structure-activity relationships. This study suggests that hydroxamates may serve as a general scaffold for developing metal-mediated inhibitors against protein tyrosine kinases. To the best of our knowledge, this is the first report of designing metal-mediated inhibitors against a protein tyrosine kinase by targeting a metal binding site.

  DOI：

  10.1021/jm061058c
• 作为产物：
  描述：

  Fmoc-L-酪氨酸 、 乙酸酐 在 吡啶 作用下， 生成 Fmoc-O-乙酰基-L-酪氨酸
  参考文献：
  名称：

  Design and Evaluation of Hydroxamate Derivatives as Metal-Mediated Inhibitors of a Protein Tyrosine Kinase

  摘要：

  Protein tyrosine kinases use two Mg2+ ions as cofactors in catalysis, one as the ATP-Mg complex (M1) and the other as an essential activator (M2). The M2-binding site has high affinity for transition metal cations such as cobalt and zinc. Taking advantage of this high affinity, we examined hydroxamates as metal-mediated inhibitors against C-terminal Src kinase (Csk), a protein tyrosine kinase. Of a small group of amino acid hydroxamates, tyrosine and phenylalanine hydroxamates inhibited Csk activity only in the presence of Co2+. Four classes of phenylalanine and tyrosine hydroxamate derivatives were synthesized and evaluated as metal-mediated inhibitors of Csk, leading to improved inhibition and a better understanding of the structure-activity relationships. This study suggests that hydroxamates may serve as a general scaffold for developing metal-mediated inhibitors against protein tyrosine kinases. To the best of our knowledge, this is the first report of designing metal-mediated inhibitors against a protein tyrosine kinase by targeting a metal binding site.

  DOI：

  10.1021/jm061058c

文献信息

• Delivering bioactive cyclic peptides that target Hsp90 as prodrugs
  作者：Yuantao Huo、Laura K. Buckton、Jack L. Bennett、Eloise C. Smith、Frances L. Byrne、Kyle L. Hoehn、Marwa N. Rahimi、Shelli R. McAlpine

  DOI：10.1080/14756366.2019.1580276

  日期：2019.1.1

  removed by liver microsomes or in-vivo and their presence decreased target binding affinity (IC50 of ≥10 µM). Thus, unlike small molecules, peptide masking groups cannot be predictably removed; their removal is related to the 3-D conformation. O-acetyl groups were cleaved but are labile, increasing challenges during synthesis. Utilising acetyl groups coupled with mono-methylated amines may decrease

  抽象的 肽类药物开发面临的最具挑战性的问题是生产一种具有最佳物理特性，同时又能保持靶标结合亲和力的分子。用可以在细胞内去除的保护基团掩盖的肽会产生可渗透细胞的肽，理论上可以保持其生物活性。描述了使用（a）O-烷基，（b）N-烷基和（c）乙酰基掩盖的一系列前药，以及它们对Hsp90的结合亲和力。烷基部分将化合物的渗透率P app从3.3增加到5.6，但是烷基不能被肝微粒体或体内去除，并且它们的存在降低了靶标结合亲和力（IC 50≥10 µM）。因此，与小分子不同，肽掩蔽基团无法预测地被去除；它们的去除与3-D构象有关。O-乙酰基被裂解但不稳定，在合成过程中增加了挑战。利用乙酰基与单甲基化胺偶联可以降低肽的极性，同时保持结合亲和力。
• Design and Evaluation of Hydroxamate Derivatives as Metal-Mediated Inhibitors of a Protein Tyrosine Kinase
  作者：Xianfeng Gu、Yuehao Wang、Anil Kumar、Guofeng Ye、Keykavous Parang、Gongqin Sun

  DOI：10.1021/jm061058c

  日期：2006.12.1

  Protein tyrosine kinases use two Mg2+ ions as cofactors in catalysis, one as the ATP-Mg complex (M1) and the other as an essential activator (M2). The M2-binding site has high affinity for transition metal cations such as cobalt and zinc. Taking advantage of this high affinity, we examined hydroxamates as metal-mediated inhibitors against C-terminal Src kinase (Csk), a protein tyrosine kinase. Of a small group of amino acid hydroxamates, tyrosine and phenylalanine hydroxamates inhibited Csk activity only in the presence of Co2+. Four classes of phenylalanine and tyrosine hydroxamate derivatives were synthesized and evaluated as metal-mediated inhibitors of Csk, leading to improved inhibition and a better understanding of the structure-activity relationships. This study suggests that hydroxamates may serve as a general scaffold for developing metal-mediated inhibitors against protein tyrosine kinases. To the best of our knowledge, this is the first report of designing metal-mediated inhibitors against a protein tyrosine kinase by targeting a metal binding site.