(2S)-2-氨基-5-[(N'-丙-2-烯基甲脒基)氨基]戊酸 | 139461-37-3

• 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: (2S)-2-氨基-5-[(N'-丙-2-烯基甲脒基)氨基]戊酸
• 中文别名: 碳杂酰苯胺酸,m-甲基-,苯甲基酯(6CI)
• 英文名称: Nω-allyl-L-arginine
• 英文别名: Nw-allyl-L-arginine；omega-N-Allylarginine；(2S)-2-amino-5-[[amino-(prop-2-enylamino)methylidene]amino]pentanoic acid
• CAS: 139461-37-3
• 化学式: C₉H₁₈N₄O₂
• 分子量: 214.268
• InChiKey: ZPQWZDPOLXVMOU-ZETCQYMHSA-N

物化性质

• 沸点：
  367.8±52.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.2
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  114
• 氢给体数：
  4
• 氢受体数：
  4

制备方法与用途

Nω-烯丙基-L-精氨酸是牛脑一氧化氮合酶（nNOS）的竞争性可逆抑制剂，能够以时间依赖性方式使NNO失活。此外，它也是一种底物，可以生成L-精氨酸、丙烯醛和水。

反应信息

• 作为反应物：
  描述：

  (2S)-2-氨基-5-[(N'-丙-2-烯基甲脒基)氨基]戊酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 N^α-acetyl-N^G-allyl-L-arginine methyl ester acetate
  参考文献：
  名称：

  Inhibition of Bovine Brain Nitric-Oxide Synthase by α-Amino and α-Carboxyl Derivatives of NG-Allyl-L-Arginine

  摘要：

  Three derivatives of the mechanism-based inhibitor N-G-allyl-L-arginine, designed to eliminate the effect of charge on the alpha-functional groups, were synthesized and tested as inhibitors of purified bovine brain nitric oxide synthase. The inhibitory properties of N-G-allyl-L-arginine, N-G-allyl-L-arginine methyl ester, N-G-acetyl-N-G-allyl-L-arginine, and N-alpha-acetyl-N-G-allyl-L-arginine methyl ester were determined in steady-state kinetic assays. The K(i)s of the four compounds were 7 +/- 1, 11 +/- 1, 147 +/- 13, and 480 +/- 45 mu M, respectively. These results demonstrate that conversion of the alpha-carboxylgroup of N-G-allyl-L-arginine to a methyl ester had only a small effect on its inhibitory properties, whereas acetylation of the alpha-amino group increased the K-i by more than an order of magnitude. Modification of both the alpha-amino and alpha-carboxyl groups increased the K-i more dramatically from 7 to 480 mu M. Derivatization of the alpha-amino and alpha-carboxyl groups of N-G-allyl-L-arginine would not be expected to alter the chemistry of inactivation by the N-G-allyl guanidine moiety, and therefore the increased K(i)s of the derivatives are probably due solely to changes in binding specificity. These data suggest that the arginine binding pocket of brain nitric oxide synthase prefers the unmodified alpha-amino group of arginine for binding, but that it can accommodate a modified alpha-carboxylate. Thus, conservative modification at the alpha-carboxyl may represent a starting point for the design and synthesis of other inhibitors targeted at nitric oxide synthase. (C) 1995 Academic Press, Inc.

  DOI：

  10.1006/bioo.1995.1012
• 作为产物：
  描述：

  (S)-tert-butyl 5-(2-allyl-3-(tert-butoxycarbonyl)guanidino)-2-((tert-butoxycarbonyl)amino)pentanoate 在 三氟乙酸 作用下， 反应 1.0h， 生成 (2S)-2-氨基-5-[(N'-丙-2-烯基甲脒基)氨基]戊酸
  参考文献：
  名称：

  A General Procedure for Synthesis ofN^G-Alkyl, andN^G-Aryl-L-Arginines as Potential Nitric Oxide Synthase inhibitors

  摘要：

  AbstractA general procedure for the synthesis of NG‐alkyl, and NG‐aryl‐L‐arginines with relatively high overall yield is reported. The key step involved the coupling of protected L‐ornithine 4 with isothiourea 7 to give the fully protected NG‐aryl‐L‐arginine derivative 8. Subsequent deprotection of 8 in acidic condition provided the final target compound 9 with an overall yield of more than 80%.

  DOI：

  10.1002/jccs.199800083

文献信息

• Mechanism of Inactivation of Neuronal Nitric Oxide Synthase by <i>N</i>^ω-Allyl-<scp>l</scp>-Arginine
  作者：Henry Q. Zhang、Robert P. Dixon、Michael A. Marletta、Dejan Nikolic、Richard Van Breemen、Richard B. Silverman

  DOI：10.1021/ja964160f

  日期：1997.11.1

  Nω-Allyl-l-arginine is shown to be a competitive reversible inhibitor and time-dependent inactivator of bovine brain nitric oxide synthase (nNOS). The enzyme is protected against inactivation by the presence of the substrate, the absence of O2, or if NADP+ is substituted for NADPH. The NADPH absorption spectrum is converted to that of NADP+ concomitant with inactivation. The latter two results indicate that

  Nω-烯丙基-l-精氨酸被证明是牛脑一氧化氮合酶 (nNOS) 的竞争性可逆抑制剂和时间依赖性灭活剂。底物的存在、O2 的不存在或 NADP+ 被 NADPH 取代，可保护酶免于失活。NADPH 吸收光谱被转换为伴随失活的 NADP+ 吸收光谱。后两个结果表明灭活需要氧化还原化学。Nω-烯丙基-Nω-羟基-l-精氨酸被合成并显示为nNOS的竞争性抑制剂和时间依赖性灭活剂，表明它是灭活过程中的可行中间体。用 Nω-烯丙基-[14C]-l-精氨酸或 Nω-[3H] 烯丙基-l-精氨酸灭活 nNOS，然后进行凝胶过滤或透析，不会导致与酶结合的放射性。分光光度法和 HPLC 显示血红素在灭活过程中被修饰为四种不同的物种。电感耦合等离子体原子发射分光光度法是...
• An Improved Synthesis of N^G-Allyl-(L)-Arginine
  作者：Michael S. Bernatowicz、Gary R. Matsueda

  DOI：10.1080/00397919308009824

  日期：1993.3.1

  A novel, more efficient and practical synthesis of the title compound, recently reported as a potent inhibitor of nitric oxide synthase is described. Reaction of (L)-ornithine with 1H-pyrazole-N-allyl-1-carboxamidine allowed facile isolation of the title product in 70% yield.
• NG-allyl- and NG-cyclopropyl-L-arginine: two novel inhibitors of macrophage nitric oxide synthase
  作者：Norman M. Olken、Michael A. Marletta

  DOI：10.1021/jm00084a020

  日期：1992.3

  N(G)-Methyl-L-arginine has recently been shown to inactivate the inducible murine macrophage nitric oxide (.NO) synthase (Olken, N. M.; Rusche, K. M.; Richards, M. K.; Marletta, M. A. Biochem. Biophys. Res. Commun. 1991, 177, 828-833). N(G)-Allyl-L-arginine and N(G)-cyclopropyl-L-arginine were synthesized as potential mechanism-based enzyme inhibitors to exploit the chemistry presumed to occur at the active site. N(G)-Cyclopropyl-L-arginine was found to be a potent reversible inhibitor with a K(i) = 7.7-mu-M. N(G)-Allyl-L-arginine was found to be both a potent reversible (K(i) = 2.1-mu-M) and irreversible inhibitor of the enzyme. This irreversible inhibition demonstrated pseudo-first-order inactivation kinetics with k(inact) = 0.026 min-1 and K(I) = 3.4-mu-M. Stereospecific protection of the inactivation was afforded by L-arginine, and saturability of the inactivation rate was observed. Our studies indicate that both reversible and irreversible inhibition of the inducible .NO synthease can be achieved with relatively simple modifications of the substrate L-arginine.
• Deuterium isotope effects and product studies for the oxidation of N ω -allyl- l -arginine and N ω -allyl- N ω -hydroxy- l -arginine by neuronal nitric oxide synthase
  作者：Jung-Mi Hah、Linda J Roman、Richard B Silverman

  DOI：10.1016/s0968-0896(00)00154-1

  日期：2000.8

  The nitric oxide synthases (NOS), which require heme, tetrahydrobiopterin, FMN, FAD, and NADPH, catalyze the O-2-dependent conversion of L-arginine to L-citrulline and nitric oxide. N-omega-Allyl-L-arginine, a mechanism-based inactivator of neuronal NOS, also is a substrate, producing L-arginine, acrolein, and H2O (Zhang, H. Q., Dixon, R. P.; Marletta, R I. A.; Nikolic, D.; Van Breemen, R.; Silverman, R. B. J. Am. Chem. SOC. 1997, 119, 10888). Two possible mechanisms for this turnover an proposed, one initiated by allyl C-I-I bond cleavage and the other by guanidino N-H cleavage, and these mechanisms are investigated with the use of N omega-allyl-L-arginine (1), N-omega-[1,1-H-2(2)]allyl-L-arginine (7), N-omega-allyl-L-hydroxy-L-alginine (2) and N-omega-[1,1-H-2(2)]allyl-N-omega-hydroxy-L-arginine (8) as substrates. Significant isotope effects on the two kinetic parameters, k(cat) and k(cat)/k(m) are observed in case of 1 and 7 during turnover, but not with 2 and 8. No kinetic isotope effects are observed for either compound in their role as inactivators. These results support a mechanism involving initial CH bond cleavage of N-omega-allyl-L-arginine followed by hydroxylation and beakdown to products. (C) 2000 Published by Elsevier Science Ltd.
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.