N-(N'-acetyl-L-phenylalanyl)-γ-aminocrotonic acid | 139200-28-5

• 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: N-(N'-acetyl-L-phenylalanyl)-γ-aminocrotonic acid
• 英文别名: Methyl 4-((N-acetylphenylalanyl)amino)but-2-enoate；(E)-4-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]but-2-enoic acid
• CAS: 139200-28-5
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: ASUSNOUQHQMQFW-LJLILKBBSA-N

物化性质

• 沸点：
  679.9±55.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(N'-acetyl-L-phenylalanyl)-γ-aminocrotonic acid 在 N-甲基吗啉 、 ammonium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 0.03h， 生成 N-(N'-acetyl-L-phenylalanyl)-γ-aminocrotonamide
  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
• 作为产物：
  描述：

  N-乙酰-L-苯丙氨酸 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 2.03h， 生成 N-(N'-acetyl-L-phenylalanyl)-γ-aminocrotonic acid
  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

• Structure-activity relationships for inhibition of papain by peptide Michael acceptors
  作者：Siming Liu、Robert P. Hanzlik

  DOI：10.1021/jm00084a012

  日期：1992.3

  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.