D-鸟氨酸 | 348-66-3

• 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: D-鸟氨酸
• 英文名称: D-ornithine
• 英文别名: ornithine；D-Orn；L-ornithine；(R)-ornithine；(2R)-2,5-diaminopentanoic acid
• CAS: 348-66-3
• 化学式: C₅H₁₂N₂O₂
• mdl: MFCD06229535
• 分子量: 132.162
• InChiKey: AHLPHDHHMVZTML-SCSAIBSYSA-N

物化性质

• 熔点：
  140 °C
• 沸点：
  308.7±32.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 碰撞截面：
  126.74 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  89.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  D-鸟氨酸 在 R₂₇₉A mutant 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.08h， 生成 N5-hydroxy-D-ornithine
  参考文献：
  名称：

  Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA

  摘要：

  Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the K-D values, as no major changes on the k(cat) or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP(+) in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbapap.2014.02.005
• 作为产物：
  描述：

  (3R,9R)-2,8-dioxo-1,7-diazacyclododecane-3,9-diamine 在 盐酸 、 水 作用下， 反应 4.0h， 生成 D-鸟氨酸
  参考文献：
  名称：

  Cyclic Dipeptide ofD-Ornithine Obtained from the Dobsonfly,Protohermes grandisThunberg

  摘要：

  从多臂蝇幼虫（Protohermes grandis Thunberg）甲醇提取物的水溶性部分中分离出了一种新化合物。通过使用高效液相色谱法、二维核磁共振法和场解吸质谱法进行手性分析，证实这种新型化合物具有一个 12 元环，是 d-ornithine 的环状二肽。

  DOI：

  10.1271/bbb.90090

文献信息

• Synthesis and Activity of 6-Substituted Purine Linker Amino Acid Immunostimulants
  作者：Boulos Zacharie、Lyne Gagnon、Giorgio Attardo、Timothy P. Connolly、Yves St-Denis、Christopher L. Penney

  DOI：10.1021/jm960844m

  日期：1997.8.1

  Further, this potent in vitro activity was reflected as a significant increase in CTL cell number in vivo. However, immunophenotyping of some of the other equipotent compounds did not reveal a parallel relative increase in CTLs in vivo. It was difficult to formulate a rigorous structure-activity relationship based on in vitro CTL activity. Nevertheless, the activity was dependent upon the nature of

  合成了一系列6-取代的嘌呤基烷氧基羰基氨基酸，并评估了它们刺激细胞毒性T淋巴细胞（CTL）和混合淋巴细胞反应（MLR）的能力。这些化合物中的一些，特别是[[5- [6-（N，N-二甲基氨基）嘌呤-9-基]戊氧基]-羰基] D-精氨酸（BCH-1393，4a）在体外刺激了与白介素2（IL 2）相当的CTL。BCH-1393增加了10（-9）M和10（-5）M之间的CTL反应。此外，这种有效的体外活性反映为体内CTL细胞数量的显着增加。但是，某些其他等效化合物的免疫表型化并未显示出体内CTL的平行相对增加。难以根据体外CTL活性来建立严格的构效关系。尽管如此，活性取决于嘌呤上6位取代基的性质，氨基酸的类型和立体化学，以及嘌呤和氨基酸之间的距离和空间自由度（由接头的长度和刚度定义）。这些化合物通常是无毒的，如BCH-1393所示。BCH-1393是一种有前途的免疫刺激剂，可用于需要增加CTL或TH1型应答的疾病状态。
• Synthetic Studies of Bacitracin. VIII. Synthesis of Cyclohexapeptide Moiety
  作者：Eisuke Munekata、Yoshihiro Masui、Tetsuo Shiba、Takeo Kaneko

  DOI：10.1246/bcsj.46.3187

  日期：1973.10

  For the purpose of synthesis of antibiotic bacitracin of six amino acids-membered ring formula, the following intermediate peptides, i.e., cyclo-(Nα-benzy]oxycarbonyl-l-lysyl-Nδ-cyclopentyloxycarbonyl-d-ornithyl-l-isojeucyl-d-phenylalanyl-l-histidyl-α-methyl-l-aspartyl) (III) and Nα-benzyloxycarbonyl-Nε-t-butyloxycarbonyl-l-lysyl-Nδ-cyclopentyloxycarbonyl-d-ornithyl-l-isoleucyl-d-phenylalanyl-Nim-benzyl-l-histidyl-l-aspartyl-d-isoasparagine benzyl ester (IV) were prepared. In this synthesis, cyclopentyloxycarbonyl group was introduced to protect δ-amino group of ornithine residue and cleavability of this protecting group for hydrogen fluoride was investigated.

  为了合成具有六个氨基酸成员环结构的抗生素巴西霉素，制备了以下中间肽，即环状(Nα-苄氧羰基-l-赖氨酸-Nδ-环戊基氧羰基-d-鸟氨酸-l-异亮氨酸-d-苯丙氨酸-l-组氨酸-α-甲基-l-天冬氨酸)(III)和Nα-苄氧羰基-Nε-t-丁氧羰基-l-赖氨酸-Nδ-环戊基氧羰基-d-鸟氨酸-l-异亮氨酸-d-苯丙氨酸-Nim-苄基-l-组氨酸-l-天冬氨酸-d-异天冬氨酸苄酯(IV)。在此合成中，引入了环戊基氧羰基基团以保护鸟氨酸残基的δ-氨基基团，并研究了该保护基团在氟化氢作用下的可裂解性。
• Lysine racemase from a lactic acid bacterium, Oenococcus oeni: structural basis of substrate specificity
  作者：Shiro Kato、Hisashi Hemmi、Tohru Yoshimura

  DOI：10.1093/jb/mvs120

  日期：2012.12

  Oenococcus oeni, a lactic acid bacterium, possesses a lysine racemase, which has a specific activity towards basic amino acids. A comparison of amino acid residues around the active site suggested that Ile222 and Tyr354 of the Geobacillus stearothermophilus alanine racemase, which shares 60% sequence similarity with lysine racemase, were replaced by Thr224 and Trp355 in the O. oeni lysine racemase. T224I/W355Y double mutations significantly decreased the activity of lysine racemase, whereas I222T/Y354W double mutations endowed alanine racemase with lysine racemization activity. These results suggest that the two residues play an important role in lysine racemization.

  Oenococcus oeni这种乳酸菌拥有一种赖氨酸消旋酶，该酶对碱性氨基酸具有特定的活性。通过比较活性位点周围的氨基酸残基，发现与赖氨酸消旋酶具有60%序列相似性的Geobacillus stearothermophilus丙氨酸消旋酶中的Ile222和Tyr354，在O. oeni赖氨酸消旋酶中被Thr224和Trp355取代。T224I/W355Y双突变显著降低了赖氨酸消旋酶的活性，而I222T/Y354W双突变则赋予丙氨酸消旋酶赖氨酸消旋化的活性。这些结果表明，这两个残基在赖氨酸消旋化中起着重要作用。
• Staphyloferrin A as siderophore-component in fluoroquinolone-based Trojan horse antibiotics
  作者：Stephen J. Milner、Alexandra Seve、Anna M. Snelling、Gavin H. Thomas、Kevin G. Kerr、Anne Routledge、Anne-Kathrin Duhme-Klair

  DOI：10.1039/c3ob40162f

  日期：——

  A series of fluoroquinolone conjugates was synthesised by linking the carboxylic acid functionality of the carboxylate-type siderophore staphyloferrin A and its derivatives to the piperazinyl nitrogen of ciprofloxacin and norfloxacin via amide bond formation. Four siderophore–drug conjugates were screened against a panel of bacteria associated with infection in humans. Whilst no activity was found against ciprofloxacin- or norfloxacin-resistant bacteria, one of the conjugates retained antibacterial activity against fluoroquinolone-susceptible strains although the structure of its lysine-based siderophore component differs from that of the natural siderophore staphyloferrin A. In contrast, three ornithine-based siderophore conjugates showed significantly reduced activity against strains that are susceptible to their respective parent fluoroquinolones, regardless of the type of fluoroquinolone attached or chirality at the ornithine Cα-atom. The loss of potency observed for the (R)- and (S)-ornithine-based ciprofloxacin conjugates correlates with their reduced inhibitory activity against the target enzyme DNA gyrase.

  一系列氟喹诺酮类缀合物通过将羧酸盐型铁载体分子的羧酸功能基团——葡萄球菌素A及其衍生物与环丙沙星和诺氟沙星的哌嗪基氮原子通过酰胺键连接而合成。筛选了四种铁载体-药物缀合物对与人类感染相关的一组细菌的作用。尽管对耐环丙沙星或诺氟沙星的细菌没有活性，但其中一个缀合物仍保留了对氟喹诺酮敏感菌株的抗菌活性，尽管其赖氨酸基铁载体部分的结构与天然铁载体葡聚糖素A不同。相比之下，三种鸟氨酸基铁载体缀合物对其各自母体氟喹诺酮敏感菌株的活性显著降低，不论所连接的氟喹诺酮类型或鸟氨酸Cα原子上的手性如何。观察到的(R)-和(S)-鸟氨酸基环丙沙星缀合物的效价损失与其对目标酶DNA促旋酶的抑制活性降低相关。
• Synthesis and activity profiles of novel cyclic opioid peptide monomers and dimers
  作者：Peter W. Schiller、Thi M. D. Nguyen、Carole Lemieux、Louise A. Maziak

  DOI：10.1021/jm00150a005

  日期：1985.12

  13-membered ring) was shown to be one of the most selective mu-receptor ligands reported to date, whereas the corresponding cyclic dimer, (H-Tyr-D-Orn-Phe-Asp-NH2)2 (1a), was nonselective. The difference in receptor selectivity observed between 1 and 1a is a consequence of the different conformational constraints present in the cyclic monomer and dimer. In contrast to 1, the conformationally less restricted

  通过在Orn（或Lys）和Asp（或Glu）残基的侧链氨基和羧基之间形成酰胺键，获得了H-Tyr-D-Xxx-Phe-Yyy-NH2型新的环状阿片肽类似物家族在肽序列的2和4位被取代。肽是完全通过固相技术合成的，除环状单体外，由于位点间反应，在苯甲基胺树脂上的环化反应还会产生侧链连接的反平行环状二聚体。在基于鼠脑膜上对mu和δ阿片类受体选择性放射性标记的置换的结合研究中，高刚性环状单体H-Tyr-D-Orn-Phe-Asp-NH2（1）（含13元环）被证明是迄今为止报道的最具选择性的mu受体配体之一，而相应的环状二聚体，（H-Tyr-D-Orn-Phe-Asp-NH2）2（1a）是非选择性的。在1a和1a之间观察到的受体选择性差异是环状单体和二聚体中存在的不同构象约束的结果。与1相反，构象上受限制较少的环状类似物H-Tyr-D-Lys-Phe-Glu-NH2（3）（15元环）没有受体偏爱。