methyl N-(N'-acetyl-L-leucyl)-γ-aminocrotonate | 139200-32-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl N-(N'-acetyl-L-leucyl)-γ-aminocrotonate
• 英文别名: methyl (E)-4-[[(2S)-2-acetamido-4-methylpentanoyl]amino]but-2-enoate
• CAS: 139200-32-1
• 化学式: C₁₃H₂₂N₂O₄
• 分子量: 270.329
• InChiKey: PKAPSDKJLGWEAT-QRGHLMKCSA-N

物化性质

• 沸点：
  506.9±45.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-乙酰-L-亮氨酸 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 2.03h， 生成 methyl N-(N'-acetyl-L-leucyl)-γ-aminocrotonate
  参考文献：
  名称：

  Structure-activity relationships for inhibition of papain by peptide Michael acceptors

  摘要：

  Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH = CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH = CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain. It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/K(i). At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283 000-fold higher than the reactivity of the model thiol 3-mercaptopropionate. This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pK(a) of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions. The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain. The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain. A plot of log (k2/K(i)) for 1a-6a vs log (k(cat)/K(m)) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope of 0.83, suggesting that binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.

  DOI：

  10.1021/jm00084a012

文献信息

• Screening methods for the binding affinity of chemical entities to biological molecules and NEDD4-1 inhibitors identified by the screening methods
  申请人：Northwestern University

  公开号：US10273208B2

  公开（公告）日：2019-04-30

  Disclosed are methods for preparing and screening for an inhibitor of the activity of a biological molecule having a catalytic or non-catalytic cysteine residue. The methods including preparing a library of candidate inhibitor molecules by conjugating an electrophile to a plurality of drug molecules where the library of candidate inhibitor molecules thus formed react with cysteine residues. The library of candidate inhibitor molecules then may be reacted with the biological molecule to identify those inhibitor molecule that react with the catalytic or non-catalytic cysteine residue of the biological molecule in order to identify an inhibitor of the biological molecule.

  本发明公开了制备和筛选具有催化或非催化半胱氨酸残基的生物分子活性抑制剂的方法。这些方法包括制备候选抑制剂分子库，方法是将亲电子体与多个药物分子共轭，由此形成的候选抑制剂分子库与半胱氨酸残基发生反应。然后可将候选抑制剂分子库与生物分子反应，以确定那些与生物分子的催化或非催化半胱氨酸残基反应的抑制剂分子，从而确定生物分子的抑制剂。
• SCREENING METHODS FOR THE BINDING AFFINITY OF CHEMICAL ENTITIES TO BIOLOGICAL MOLECULES AND NEDD4-1 INHIBITORS IDENTIFIED BY THE SCREENING METHODS
  申请人：NORTHWESTERN UNIVERSITY

  公开号：US20160016893A1

  公开（公告）日：2016-01-21

  Disclosed are methods for screening for the binding affinity of chemical entities to other bioactive molecules. The screened chemical entities may be utilized in pharmaceutical composition or therapeutic methods for treating disease or disorders associated with the bioactive molecules including NEDD4-1.
• US9586890B2
  申请人：——

  公开号：US9586890B2

  公开（公告）日：2017-03-07