R-(-)-Histidinmethylester

• 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: R-(-)-Histidinmethylester
• 英文别名: methyl (2R)-2-amino-3-(1H-imidazol-5-yl)propanoate
• 化学式: C₇H₁₁N₃O₂
• 分子量: 169.183
• InChiKey: BXRMEWOQUXOLDH-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  81
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  R-(-)-Histidinmethylester 在 Streptomyces spp. 83D₁₂ D-aminopeptidase 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 生成 D-组氨酸
  参考文献：
  名称：

  Aminolytic reaction catalyzed by d-stereospecific amidohydrolases from Streptomyces spp

  摘要：

  From investigation of 2000 soil isolates, we identified two serine-type amidohydrolases that can hydrolyze D-aminoacyl derivatives from the culture supernatant of Streptomyces species 82F2 and 83D12. The enzymes, redesignated as 82F2-DAP and 83D12-DAP, were purified for homogeneity and characterized. Each enzyme had molecular mass of approximately 40 kDa, and each showed moderate stability with respect to temperature and pH. Among hydrolytic activities toward D-aminoacyl-pNAs, the enzymes showed strict specificity toward D-Phe-pNA, but showed broad specificity toward D-aminoacyl esters. The specific activity for D-Phe-pNA hydrolysis of 82F2-DAP was ten-fold higher than that of 83D12-DAP. As a second function, each enzyme showed peptide bond formation activity by its function of aminolysis reaction. Based on results of D-Phe D-Phe synthesis under various conditions, we propose a reaction mechanism for D-Phe D-Phe production. Furthermore, the enzymes exhibited peptide elongation activity, producing oligo homopeptide in a one-pot reaction. We cloned the genes encoding each enzyme, which revealed that the primary structure of each enzyme showed 30-60% identity with those of peptidases belonging to the clan SE, S12 peptidase family categorized as serine peptidase with D-stereospecificity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biochi.2011.04.020
• 作为产物：
  描述：

  甲醇 、 D-组氨酸 在 氯化亚砜 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.01h， 生成 R-(-)-Histidinmethylester
  参考文献：
  名称：

  用双（锌卟啉）镊子在客体-客体复合物中的单分子结合客体的激子耦合圆二色性表征。

  摘要：

  具有固有螺旋度的刚性-苯乙烯连接的双卟啉镊子用于一系列单位结合的胺客体分子的激子偶联圆二色性（ECCD）表征。在相对较低的镊子/胺（主体/客体）比例为1:10至1:70的范围内，观察到各种单胺的CD信号。对于产生最强CD信号的胺，发现其化学计量比为1：2。一个可能的解释是复合体中访客与访客之间的相互作用。CD信号强度与来宾之间可能的非共价结合强度之间的相关性支持了这一点，可以将其分为三组，分别显示无，中度和强反应。这种合理化的进一步支持来自分子建模。

  DOI：

  10.1002/cplu.201800564

文献信息

• Reducing Platelet Activation, Aggregation and Platelet-Stimulated Thrombosis or Blood Coagulation by Reducing Mitochondrial Respiration
  申请人：Collman James P.

  公开号：US20110301180A1

  公开（公告）日：2011-12-08

  It has been discovered that inhibiting mitochondrial respiration in platelets reduces platelet activation or platelet aggregation. Certain heterocyclic compounds significantly reduced one or more platelet functions including clumping, sticking or platelet-stimulated clotting. Thus diseases or disorders mediated by inappropriately high levels of platelet activation or platelet aggregation can be treated by administering a therapeutically effective amount of a heterocyclic compound or nonheterocyclic mitochondrial inhibitor that significantly reduces one or more platelet functions including clumping, sticking or platelet-stimulated clotting, preferably in a reversible manner.

  已经发现，在血小板中抑制线粒体呼吸可以减少血小板的激活或血小板聚集。某些杂环化合物显著降低了一个或多个血小板功能，包括凝聚、粘附或血小板刺激的凝血。因此，由血小板激活或血小板聚集水平不当高导致的疾病或疾病可以通过给予一种治疗有效量的杂环化合物或非杂环线粒体抑制剂来治疗，该化合物显著降低了一个或多个血小板功能，包括凝聚、粘附或血小板刺激的凝血，最好是以可逆的方式。
• Pharmaceuticals
  申请人：——

  公开号：US20020147229A1

  公开（公告）日：2002-10-10

  The present invention provides compounds of formula (I) 1 as well as the use of such compounds in pharmaceutical compositions and methods of treatment. The compounds described herein represent a class of TAFIla inhibitors suitable for use in treating conditions such as thrombosis, atherosclerosis, adhesions, dermal scarring, cancer, fibrotic conditions, inflammatory diseases and those conditions which benefit from maintaining or enhancing bradykinin levels in the body.

  本发明提供了式(I)1的化合物，以及这些化合物在制药组合物和治疗方法中的应用。本文描述的化合物代表了一类适用于治疗血栓形成、动脉粥样硬化、粘连、皮肤瘢痕、癌症、纤维化疾病、炎症性疾病以及那些受益于维持或增强体内激肽酶激活因子Ⅰ（TAFIla）抑制剂的疾病的化合物。
• Heterodimers of Histidine and Amantadine as Inhibitors for Wild Type and Mutant M2 Channels of Influenza A
  作者：Wenjuan Zhang、Jing Xu、Fang Liu、Chufang Li、Yanling Jie、Shaopeng Chen、Zhiyuan Li、Jinsong Liu、Ling Chen、Guochun Zhou

  DOI：10.1002/cjoc.201090242

  日期：——

  Inhibitors bearing the imidazole, adamantane and related structures were synthesized and tested against WT, S31N and S31N‐L26I mutant M2 channels. Although amantadine (1) only inhibited WT M2 channel, compound 6 containing the imidazole and adamantane groups showed good inhibitory activity to WT and mutant M2 channels. The stereochemistry and basic pKa of α‐amine are important for the activity of inhibitors

  合成了带有咪唑，金刚烷和相关结构的抑制剂，并针对WT，S31N和S31N-L26I突变M2通道进行了测试。尽管金刚烷胺（1）仅抑制WT M2通道，但含有咪唑和金刚烷基团的化合物6对WT和突变M2通道显示出良好的抑制活性。α-胺的立体化学和碱性p K a对抑制剂的活性很重要，我们的数据表明，天然组氨酸的衍生物对M2通道的活性比非天然组氨酸的衍生物高。我们当前结果的意义在于，我们已经建立了一种针对WT和突变型M2通道针对甲型流感的药物发现的前瞻性策略。
• Intracellular Reactions Promoted by Bis(histidine) Miniproteins Stapled Using Palladium(II) Complexes
  作者：Soraya Learte‐Aymamí、Cristian Vidal、Alejandro Gutiérrez‐González、José L. Mascareñas

  DOI：10.1002/anie.202002032

  日期：2020.6.2

  The generation of catalytically active metalloproteins inside living mammalian cells is a major research challenge at the interface between catalysis and cell biology. Herein we demonstrate that basic domains of bZIP transcription factors, mutated to include two histidine residues at i and i+4 positions, react with palladium(II) sources to generate catalytically active, stapled pallado-miniproteins

  活的哺乳动物细胞内催化活性金属蛋白的产生是催化和细胞生物学之间的主要研究挑战。在本文中，我们证明了bZIP转录因子的基本结构域，被突变为在i和i + 4位置包括两个组氨酸残基，与钯（II）源反应生成催化活性的吻合的帕拉多小蛋白。所得的受约束肽可有效地内化到活的哺乳动物细胞中，在其中它们进行钯促进的去炔丙基化反应而无需细胞固定。对照实验证实了获得细胞内反应性需要肽支架和钯钉。
• Development of an <i>N</i>-Acyl Amino Acid That Selectively Inhibits the Glycine Transporter 2 To Produce Analgesia in a Rat Model of Chronic Pain
  作者：Shannon N. Mostyn、Tristan Rawling、Sarasa Mohammadi、Susan Shimmon、Zachary J. Frangos、Subhodeep Sarker、Arsalan Yousuf、Irina Vetter、Renae M. Ryan、Macdonald J. Christie、Robert J. Vandenberg

  DOI：10.1021/acs.jmedchem.8b01775

  日期：2019.3.14

  Inhibitors that target the glycine transporter 2, GlyT2, show promise as analgesics, but may be limited by their toxicity through complete or irreversible binding. Acyl-glycine inhibitors, however, are selective for GlyT2 and have been shown to provide analgesia in animal models of pain with minimal side effects, but are comparatively weak GlyT2 inhibitors. Here, we modify the simple acyl-glycine by

  靶向甘氨酸转运蛋白 2、GlyT2 的抑制剂显示出作为镇痛剂的前景，但可能会通过完全或不可逆的结合而受到毒性的限制。然而，酰基甘氨酸抑制剂对 GlyT2 具有选择性，并且已被证明可在动物疼痛模型中提供镇痛作用，且副作用最小，但 GlyT2 抑制剂的作用相对较弱。在这里，我们通过合成具有一系列 l 和 d 构型的氨基酸头基的脂质类似物来修饰简单的酰基甘氨酸，以产生纳摩尔亲和力的选择性 GlyT2 抑制剂。强效抑制剂油酰-d-赖氨酸 (33) 对人和大鼠血浆和肝微粒体的降解也具有抗性，并且在大鼠腹腔注射后迅速吸收并容易穿过血脑屏障。