(2S,4S)-5-hydroxyleucine | 118758-46-6

• 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: (2S,4S)-5-hydroxyleucine
• 英文别名: (2S,4S)-2-amino-5-hydroxy-4-methylpentanoic acid
• CAS: 118758-46-6
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: SDCAQJCTUOFAKD-WHFBIAKZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4S)-5-hydroxyleucine 在 聚甘氨酸 NosE gene from Escherichia coli 、 β-烟酰胺腺嘌呤二核苷酸 、 zinc(II) sulfate 作用下， 以 水 为溶剂， 生成 (2S,4S)-4-methyl-3,4-dihydro-2H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  Biosynthesis of 4-Methylproline in Cyanobacteria:  Cloning of nosE and nosF Genes and Biochemical Characterization of the Encoded Dehydrogenase and Reductase Activities

  摘要：

  The biosynthesis of the unusual amino acid 4-methylproline in the Nostoc genus of cyanobacteria was investigated on the genetic and enzymatic level. Two genes involved in the biosynthesis were cloned and the corresponding enzymes, a zinc-dependent long-chain dehydrogenase and a Delta(1)-pyrroline-5-carboxylic acid (P5C) reductase homologue, were overexpressed in Escherichia coli and biochemically characterized. Putative substrates were synthesized to test enzyme substrate specificities, and deuterium labeling studies were carried out to reveal the stereospecificities of the enzymatic reactions with respect to the substrates as well as to the coenzymes.

  DOI：

  10.1021/jo026479q
• 作为产物：
  描述：

  L-亮氨酸 在 L-Leu 5-hydroxylase 、 2-氧代-戊二酸离子(2-) 、 铁粉 作用下， 反应 0.33h， 生成 (2S,4S)-5-hydroxyleucine
  参考文献：
  名称：

  重新利用非血红素铁羟化酶以通过叠氮基团协助实现催化腈安装

  摘要：

  三种单核非血红素铁和 2-酮戊二酸依赖性酶，l-Ile 4-羟化酶、l-Leu 5-羟化酶和多氧辛二羟化酶，先前已报道可催化 l-异亮氨酸、l-亮氨酸和 l-α-氨基的羟基化-δ-氨基甲酰基羟基戊酸（ACV）。在这项研究中，我们表明这些酶可以容纳亮氨酸异构体并催化区域特异性羟基化。在这些结果的基础上，作为概念验证，我们证明了反应的结果可以通过在基板内安装辅助组来重定向。具体来说，当引入叠氮基时，这些酶可以催化非天然腈基的安装，而不是经典的羟基化。该反应很可能通过 Fe(IV)-氧类物质激活 CH 键进行，然后形成叠氮导向的 C≡N 键。

  DOI：

  10.1021/jacs.8b13906

文献信息

• 3-Hydroxylysine, a Potential Marker for Studying Radical-Induced Protein Oxidation
  作者：Bénédicte Morin、William A. Bubb、Michael J. Davies、Roger T. Dean、Shanlin Fu

  DOI：10.1021/tx980118h

  日期：1998.11.1

  gamma-Irradiation of several amino acids (Val, Leu, lie, Lys, Pro, and Glu) in the presence of O-2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO. attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3-hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4-hydroxyhexanoic acid], (2S,5R)-5-hydroxylysine [(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5-hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu-Phe) and proteins (BSA and histone H1) exposed to HO ./O-2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.
• Belokon', Yuri N.; Bulychev, Aleksandr G.; Pavlov, Viacheslav A., Journal of the Chemical Society. Perkin transactions I, 1988, p. 2075 - 2084
  作者：Belokon', Yuri N.、Bulychev, Aleksandr G.、Pavlov, Viacheslav A.、Fedorova, Eugenia B.、Tsyryapkin, Vladimir A.、et al.

  DOI：——

  日期：——
• ENGLISCH-PETERS, SABINE, TETRAHEDRON, 45,(1989) N9, C. 6127-6134
  作者：ENGLISCH-PETERS, SABINE

  DOI：——

  日期：——
• [EN] L-LEUCINE HYDROXYLASE AND DNA ENCODING THE ENZYME<br/>[FR] L-LEUCINE HYDROXYLASE ET ADN CODANT POUR L'ENZYME
  申请人：MEIJI SEIKA KAISHA

  公开号：WO2008013262A1

  公开（公告）日：2008-01-31

  [EN] Disclosed are: a novel protein having an L-leucine hydroxylase activity, i.e., an activity of converting L-leucine into (2S,4S)-5-hydroxyleucine; DNA encoding the protein; recombinant DNA containing the DNA; a transformant carrying the recombinant DNA; the protein using the transformant; and a method for producing (2S,4S)-5-hydroxyleucine. It becomes possible to provide a method for producing (2S,4S)-5-hydroxyleucine, which is a substance expected to be used as a starting material for the production of a useful substance such as a pharmaceutical agent, by utilizing an organism, an enzyme or the like. The method enables to produce (2S,4S)-5-hydroxyleucine at high efficiency.
  [FR] La présente invention concerne une nouvelle protéine présentant une activité L-leucine hydroxylase, c'est-à-dire une activité de conversion de la L-leucine en (2S,4S)-5-hydroxyleucine, ainsi qu'un ADN codant pour la protéine, un ADN recombinant contenant l'ADN, un transformant portant l'ADN recombinant, la protéine utilisant le transformant et un procédé permettant de produire la (2S,4S)-5-hydroxyleucine. Il devient possible d'élaborer un procédé permettant de produire la (2S,4S)-5-hydroxyleucine, une substance prévue pour être utilisée comme matériau de départ pour la production d'une substance utile telle qu'un agent pharmaceutique, en utilisant un organisme, une enzyme ou des éléments analogues. Le procédé permet de produire la (2S,4S)-5-hydroxyleucine avec une grande efficacité.
• Repurposing Nonheme Iron Hydroxylases To Enable Catalytic Nitrile Installation through an Azido Group Assistance
  作者：Madison Davidson、Meredith McNamee、Ruixi Fan、Yisong Guo、Wei-chen Chang

  DOI：10.1021/jacs.8b13906

  日期：2019.2.27

  the substrate. Specifically, instead of canonical hydroxylation, these enzymes can catalyze non-native nitrile group installation when an azido group is introduced. The reaction is likely to proceed through C-H bond activation by an Fe(IV)-oxo species, followed by azido-directed C≡N bond formation. These results offer a unique opportunity to investigate and expand the reaction repertoire of Fe/2OG enzymes

  三种单核非血红素铁和 2-酮戊二酸依赖性酶，l-Ile 4-羟化酶、l-Leu 5-羟化酶和多氧辛二羟化酶，先前已报道可催化 l-异亮氨酸、l-亮氨酸和 l-α-氨基的羟基化-δ-氨基甲酰基羟基戊酸（ACV）。在这项研究中，我们表明这些酶可以容纳亮氨酸异构体并催化区域特异性羟基化。在这些结果的基础上，作为概念验证，我们证明了反应的结果可以通过在基板内安装辅助组来重定向。具体来说，当引入叠氮基时，这些酶可以催化非天然腈基的安装，而不是经典的羟基化。该反应很可能通过 Fe(IV)-氧类物质激活 CH 键进行，然后形成叠氮导向的 C≡N 键。