α-N-(tert-butoxycarbonyl)-N^G-hydroxy-N^G-methyl-N^G'-(tert-butoxycarbonyl)-L-arginine tert-butyl ester | 147527-32-0

• 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: α-N-(tert-butoxycarbonyl)-N^G-hydroxy-N^G-methyl-N^G'-(tert-butoxycarbonyl)-L-arginine tert-butyl ester
• 英文别名: tert-butyl (2S)-5-[[[hydroxy(methyl)amino]-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 147527-32-0
• 化学式: C₂₁H₄₀N₄O₇
• 分子量: 460.571
• InChiKey: RQQXGRLJYUOHPH-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  α-N-(tert-butoxycarbonyl)-N^G-hydroxy-N^G-methyl-N^G'-(tert-butoxycarbonyl)-L-arginine tert-butyl ester 、 三氟乙酸 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 以23%的产率得到L-N^G-hydroxy-N^G-methylarginine bistrifluoroacetate salt
  参考文献：
  名称：

  Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation

  摘要：

  L-N(G)-Methylarginine (NMA) is an established mechanism-based inactivator of murine macrophage nitric oxide synthase (mNOS). In this report, NMA is shown to irreversibly inhibit both mNOS (k(inact)=0.08 min-1) and there combinant constitutive brain NOS (bNOS). For both NOS isoforms, metabolism of NMA parallels that of the natural substrate L-arginine (ARG), in that it undergoes a regiospecific, NADPH-dependent hydroxylation to form L-N(G)-hydroxy-N(G)-methylarginine (NOHNMA). This intermediate then undergoes further NADPH-dependent oxidation to form L-citrulline (CIT). Authentic NOHNMA, synthesized from L-ornithine, irreversibly inhibited both mNOS(k(inact)=0.10 min-1)and bNOS in an NADPH-dependent reaction. The conversion of either NMA or NOHNMA to CIT correlated with irreversible enzyme inactivation. Thus, the data suggest that enzyme inhibition occurs as a consequence of oxidative metabolism of the intermediate, NOHNMA. A unified mechanism is proposed that accounts for NO biosynthesis from ARG, for the inactivation of NOS by NMA and for the intermediacy of hydroxylated ARG or NMA derivatives in these processes.

  DOI：

  10.1021/jm00056a009
• 作为产物：
  描述：

  α-N-(tert-butoxycarbonyl)-δ-<(N¹-(tert-butoxycarbonyl)-S-methyl)-1-isothioureido>-L-norvaline tert-butyl ester 在 palladium on activated charcoal 氢气 、 silver nitrate 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 20.0h， 生成 α-N-(tert-butoxycarbonyl)-N^G-hydroxy-N^G-methyl-N^G'-(tert-butoxycarbonyl)-L-arginine tert-butyl ester
  参考文献：
  名称：

  Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation

  摘要：

  L-N(G)-Methylarginine (NMA) is an established mechanism-based inactivator of murine macrophage nitric oxide synthase (mNOS). In this report, NMA is shown to irreversibly inhibit both mNOS (k(inact)=0.08 min-1) and there combinant constitutive brain NOS (bNOS). For both NOS isoforms, metabolism of NMA parallels that of the natural substrate L-arginine (ARG), in that it undergoes a regiospecific, NADPH-dependent hydroxylation to form L-N(G)-hydroxy-N(G)-methylarginine (NOHNMA). This intermediate then undergoes further NADPH-dependent oxidation to form L-citrulline (CIT). Authentic NOHNMA, synthesized from L-ornithine, irreversibly inhibited both mNOS(k(inact)=0.10 min-1)and bNOS in an NADPH-dependent reaction. The conversion of either NMA or NOHNMA to CIT correlated with irreversible enzyme inactivation. Thus, the data suggest that enzyme inhibition occurs as a consequence of oxidative metabolism of the intermediate, NOHNMA. A unified mechanism is proposed that accounts for NO biosynthesis from ARG, for the inactivation of NOS by NMA and for the intermediacy of hydroxylated ARG or NMA derivatives in these processes.

  DOI：

  10.1021/jm00056a009

文献信息

• Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation
  作者：Paul L. Feldman、Owen W. Griffith、Hui Hong、Dennis J. Stuehr

  DOI：10.1021/jm00056a009

  日期：1993.2

  L-N(G)-Methylarginine (NMA) is an established mechanism-based inactivator of murine macrophage nitric oxide synthase (mNOS). In this report, NMA is shown to irreversibly inhibit both mNOS (k(inact)=0.08 min-1) and there combinant constitutive brain NOS (bNOS). For both NOS isoforms, metabolism of NMA parallels that of the natural substrate L-arginine (ARG), in that it undergoes a regiospecific, NADPH-dependent hydroxylation to form L-N(G)-hydroxy-N(G)-methylarginine (NOHNMA). This intermediate then undergoes further NADPH-dependent oxidation to form L-citrulline (CIT). Authentic NOHNMA, synthesized from L-ornithine, irreversibly inhibited both mNOS(k(inact)=0.10 min-1)and bNOS in an NADPH-dependent reaction. The conversion of either NMA or NOHNMA to CIT correlated with irreversible enzyme inactivation. Thus, the data suggest that enzyme inhibition occurs as a consequence of oxidative metabolism of the intermediate, NOHNMA. A unified mechanism is proposed that accounts for NO biosynthesis from ARG, for the inactivation of NOS by NMA and for the intermediacy of hydroxylated ARG or NMA derivatives in these processes.