N⁵-isopropyl-L-glutamine | 4311-12-0

• 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: N⁵-isopropyl-L-glutamine
• 英文别名: N-isopropyl-L-glutamine；(2S)-2-amino-5-oxo-5-(propan-2-ylamino)pentanoic acid
• CAS: 4311-12-0
• 化学式: C₈H₁₆N₂O₃
• 分子量: 188.227
• InChiKey: CABXGBMKSVRWOG-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  96.9
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2924199090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  | 2-8°C |

反应信息

• 作为反应物：
  描述：

  N⁵-isopropyl-L-glutamine 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 14.67h， 生成 [(1S,2S)-1-((S)-3-Isopropylcarbamoyl-1-{(S)-1-[(S)-1-((E)-2-methanesulfonyl-vinyl)-3-methyl-butylcarbamoyl]-ethylcarbamoyl}-propylcarbamoyl)-2-methyl-butyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Optimization of Subsite Binding to the β5 Subunit of the Human 20S Proteasome Using Vinyl Sulfones and 2-Keto-1,3,4-oxadiazoles:  Syntheses and Cellular Properties of Potent, Selective Proteasome Inhibitors

  摘要：

  Beginning with the peptide sequence Cbz-Ile-Glu(OtBu)-Ala-Leu found in PSI (3), a series of vinyl sulfones (VS) were synthesized for evaluation as inhibitors of the chymotrypsin-like activity of the 20S proteasome. Variations at the key P3 position confirmed the importance of a long side chain capped with a hydrophobic group for optimal potency, consistent with a model of binding to the S3 subsite. The tert-butyl glutamic ester initially used at P3 gave plasma unstable, insoluble compounds and was replaced with the better isostere, N-beta-neopentyl asparagine. The inhibitors were shortened by replacing the N-terminal Cbz-isoleucine with a p-tosyl group without loss of potency. Small L-amino acids were used at P2, where D-substitution was not tolerated. The resulting optimized P4-P3-P2 sequence was grafted onto a novel proteasome inhibitor warhead, 2-keto-1,3,4-oxadiazoles (KOD), to produce reversible, subnanomolar proteasome inhibitors that were 1000-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-like proteasome activity. A number of compounds in both the VS and the KOD series exhibited growth inhibitory effects against the human prostate cancer cell line PC3 at submicromolar concentrations.

  DOI：

  10.1021/jm058289o
• 作为产物：
  描述：

  Γ-谷氨酰-谷氨酰胺 在 recombinant Pseudomonas nitroreducens IFO12694 γ-glutamyltranspeptidase 作用下， 反应 0.36h， 生成 N⁵-isopropyl-L-glutamine
  参考文献：
  名称：

  Molecular Cloning and Characterization of γ-Glutamyltranspeptidase fromPseudomonas nitroreducensIFO12694

  摘要：

  与其它γ-谷氨酰转肽酶（GGT）相比，来自IFO12694的铜绿假单胞菌（PnGGT）展现出更高的水解活性而非转移活性。PnGGT对大多数L-氨基酸和常在GGT转移反应中用作标准γ-谷氨酰受体的甘氨酰甘氨酸表现出极低活性。作为γ-谷氨酰受体，PnGGT的优先底物为甲胺、乙胺和异丙胺等胺类。

  DOI：

  10.1271/bbb.100199

文献信息

• [EN] AMINO ACID DERIVATIVES AND THEIR USE AS FLAVOR MODIFIERS<br/>[FR] DÉRIVÉS D'ACIDES AMINÉS ET LEUR UTILISATION EN TANT QUE MODIFICATEURS DE GOÛT
  申请人：FIRMENICH & CIE

  公开号：WO2021209345A1

  公开（公告）日：2021-10-21

  The present invention provides derivatives of glutamine of formula (I) and derivatives of arginine of formula (II), and the use of such compounds as flavor modifiers. The invention further provides the use of such derivatives of glutamine and arginine to enhance the salty and umami taste of ingestible compositions as ingestible compositions that include such derivatives of glutamine and arginine and bulking agents.

  本发明提供了公式(I)的谷氨酰衍生物和公式(II)的精氮酸衍生物，以及将这些化合物用作风味调节剂的用途。该发明进一步提供了利用这些谷氨酰和精氮酸衍生物增强可摄入组合物的咸味和鲜味的用途，作为包含这些谷氨酰和精氮酸衍生物以及增稠剂的可摄入组合物。
• [EN] NOVEL INSULIN DERIVATIVES AND THE MEDICAL USES HEREOF<br/>[FR] NOUVEAUX DÉRIVÉS D'INSULINE ET LEURS UTILISATIONS MÉDICALES
  申请人：NOVO NORDISK AS

  公开号：WO2017032798A1

  公开（公告）日：2017-03-02

  The present invention is in the therapeutic fields of drugs for medical conditions relating to diabetes. More specifically the invention relates to novel acylated derivatives of human insulin analogues. The invention also provides pharmaceutical compositions comprising such insulin derivatives, and relates to the use of such derivatives for the treatment or prevention of medical conditions relating to diabetes.

  本发明涉及与糖尿病相关的医疗药物领域。更具体地，该发明涉及人类胰岛素类似物的新型酰化衍生物。该发明还提供了包含这种胰岛素衍生物的药物组合物，并涉及使用这些衍生物治疗或预防与糖尿病相关的医疗状况。
• A Novel Catalytic Ability of γ-Glutamylcysteine Synthetase of<i>Escherichia coli</i>and Its Application in Theanine Production
  作者：Koichiro MIYAKE、Shingo KAKITA

  DOI：10.1271/bbb.90538

  日期：2009.12.23

  γ-Glutamylcysteine synthetase (γGCS, EC 6.3.2.2) catalyzes the formation of γ-glutamylcysteine from l-glutamic acid (Glu) and l-cysteine (Cys) in an ATP-dependent manner. While γGCS can use various amino acids as substrate, little is known about whether it can use non-amino acid compounds in place of Cys. We determined that γGCS from Escherichia coli has the ability to combine Glu and amines to form γ-glutamylamides. The reaction rate depended on the length of the methylene chain of the amines in the following order: n-propylamine > butylamine > ethylamine >> methylamine. The optimal pH for the reaction was narrower and more alkaline than for the reaction with an amino acid. The newly found catalytic ability of γGCS was used in the production of theanine (γ-glutamylethylamine). The resting cells of E. coli expressing γGCS, in which ATP was regenerated through glycolysis, synthesized 12.1 mm theanine (18 h) from 429 mm ethylamine.

  γ-谷氨酰半胱氨酸合成酶（γGCS，EC 6.3.2.2）以 ATP 依赖性方式催化 l-谷氨酸（Glu）和 l-半胱氨酸（Cys）形成γ-谷氨酰半胱氨酸。虽然γGCS可以使用多种氨基酸作为底物，但人们对它是否可以使用非氨基酸化合物代替Cys知之甚少。我们确定大肠杆菌中的γGCS能够将Glu和胺结合形成γ-谷氨酰胺。反应速率取决于胺的亚甲基链长度，顺序如下：正丙胺 > 丁胺 > 乙胺 >> 甲胺。与与氨基酸反应相比，该反应的最佳 pH 值更窄、碱性更强。新发现的 γGCS 催化能力被用于生产茶氨酸（γ-谷氨酰乙胺）。表达 γGCS 的大肠杆菌静息细胞通过糖酵解再生 ATP，在 18 小时内从 429 毫米乙胺中合成了 12.1 毫米茶氨酸。
• TEMPLATE-FIXED PEPTIDOMIMETICS WITH CCR10 ANTAGONISTIC ACTIVITY
  申请人：Jung Francoise

  公开号：US20120283168A1

  公开（公告）日：2012-11-08

  Novel template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected in either direction which, depending on their positions in the chain, are as defined in the description and the claims, and salts thereof, have the property to antagonize the receptor CCR10. They can be used as medicaments to treat or prevent diseases or conditions in the area of dermatological and cutaneous disorders, inflammation, allergic disorders, respiratory diseases, diseases of the gastro-intestinal tract, ophthalmic diseases, haematology and cancer. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  具有以下一般式(I)的小说模板固定β-发夹仿生肽，其中单个元素T或P是α-氨基酸残基，可以连接在任何方向上，具体取决于它们在链中的位置，如描述和索赔中所定义，及其盐，具有拮抗受体CCR10的特性。它们可用作药物，用于治疗或预防皮肤病和皮肤疾病、炎症、过敏性疾病、呼吸道疾病、胃肠道疾病、眼科疾病、血液学和癌症等领域。这些β-发夹仿生肽可以通过基于混合固相和溶液相合成策略的过程制备。
• Transformation of Isopropylamine to <scp>l</scp> -Alaninol by <i>Pseudomonas</i> sp. Strain KIE171 Involves <i>N</i> -Glutamylated Intermediates
  作者：Susana I. de Azevedo Wäsch、Jan R. van der Ploeg、Tere Maire、Alice Lebreton、Andreas Kiener、Thomas Leisinger

  DOI：10.1128/aem.68.5.2368-2375.2002

  日期：2002.5

  Pseudomonas sp. strain KIE171 was able to grow with isopropylamine or l -alaninol [ S -(+)-2-amino-1-propanol] as the sole carbon source, but not with d -alaninol. To investigate the hypothesis that l -alaninol is an intermediate in the degradation of isopropylamine, two mini-Tn 5 mutants unable to utilize both isopropylamine and l -alaninol were isolated. Whereas mutant KIE171-BI transformed isopropylamine to l -alaninol, mutant KIE171-BII failed to do so. The two genes containing a transposon insertion were cloned, and the DNA regions flanking the insertions were sequenced. Two clusters, one comprising eight ipu (isopropylamine utilization) genes ( ipuABCDEFGH ) and the other encompassing two genes ( ipuI and orf259 ), were identified. Comparisons of sequences of the deduced Ipu proteins and those in the database suggested that isopropylamine is transported into the cytoplasm by a putative permease, IpuG. The next step, the formation of γ-glutamyl-isopropylamide from isopropylamine, ATP, and l -glutamate, was shown to be catalyzed by IpuC, a γ-glutamylamide synthetase. γ-Glutamyl-isopropylamide is then subjected to stereospecific monooxygenation by the hypothetical four-component system IpuABDE, thereby yielding γ-glutamyl- l -alaninol [γ( l -glutamyl)- l -hydroxy-isopropylamide]. Enzymatic hydrolysis by a hydrolase, IpuF, was shown to finally liberate l -alaninol and to regenerate l -glutamate. No gene(s) encoding an enzyme for the next step in the degradation of isopropylamine was found in the ipu clusters. Presumably, l -alaninol is oxidized by an alcohol dehydrogenase to yield l -2-aminopropionaldehyde or it is deaminated by an ammonia lyase to propionaldehyde. Genetic evidence indicated that the aldehyde formed is then further oxidized by the hypothetical aldehyde dehydrogenases IpuI and IpuH to either l -alanine or propionic acid, compounds which can be processed by reactions of the intermediary metabolism.

  摘要 假单胞菌 菌株 KIE171 能够在异丙胺或 l -丙氨醇[ S -(+)-2-氨基-1-丙醇] 作为唯一碳源，但不能以 d -丙醇作为唯一碳源。为了研究 l -丙氨醇是异丙基胺降解过程中的一个中间体这一假设进行了研究。 5 突变体不能同时利用异丙基胺和 l -丙氨醇的中间体。而突变体 KIE171-BI 将异丙基胺转化为 l -丙氨醇。 l -丙氨醇，而突变体 KIE171-BII 却不能做到这一点。克隆了含有转座子插入的两个基因，并对插入侧翼的 DNA 区域进行了测序。两个基因簇，一个由八个 ipu (异丙基胺利用）基因 ( ipuABCDEFGH )，另一个包括两个基因 ( ipuI 和 orf259 )。对推导出的 Ipu 蛋白的序列和数据库中的序列进行比较后发现，异丙基胺是通过一种假定的渗透酶 IpuG 转运到细胞质中的。下一步是由异丙基胺、ATP 和γ-谷氨酰-异丙基酰胺形成γ-谷氨酰-异丙基酰胺。 l -γ-谷氨酰-异丙基酰胺然后由假定的四组分系统 IpuABDE 进行立体特异性单氧合反应，从而产生γ-谷氨酰-异丙基酰胺。 l -丙氨醇[γ( l -谷氨酰）- l -羟基异丙基酰胺]。研究表明，水解酶 IpuF 的酶促水解最终会释放出 l -丙氨醇，并再生出 l -谷氨酸。在 IpuF 中没有发现编码异丙基胺下一步降解酶的基因。 ipu 簇中没有发现编码异丙基胺下一步降解酶的基因。推测 l -丙氨醇被醇脱氢酶氧化，生成 l -2-氨基丙醛，或者被氨裂解酶脱氨成丙醛。遗传学证据表明，形成的醛随后会被假定的醛脱氢酶 IpuI 和 IpuH 进一步氧化，生成 l -2 -氨基丙醛或 l -2 -氨基丙醛。 l -丙氨酸或丙酸，这些化合物可通过中间代谢反应进行处理。