D-Trp-Aib | 1123071-24-8

• 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: D-Trp-Aib
• 英文别名: Alanine, D-tryptophyl-2-methyl-；2-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-2-methylpropanoic acid
• CAS: 1123071-24-8
• 化学式: C₁₅H₁₉N₃O₃
• 分子量: 289.334
• InChiKey: SHAXSXUDZJSSCN-LLVKDONJSA-N

物化性质

• 沸点：
  620.4±55.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  4

制备方法与用途

MRZ-99030 是一种 Aβ 聚集调节剂，能够通过触发非淀粉样蛋白聚集途径来减少中等毒性可溶性低聚物Aβ的数量。

反应信息

• 作为反应物：
  描述：

  D-Trp-Aib 在 sodium hydroxide 作用下， 以 水 为溶剂， 以34 g的产率得到
  参考文献：
  名称：

  [EN] CRYSTALLINE FORMS OF SOLVATES OF TRYPTOPHAN DERIVATIVES, COMPOSITIONS COMPRISING THEM AND USES THEREOF
  [FR] FORMES CRISTALLINES DE SOLVATES DE DÉRIVÉS DE TRYPTOPHANE, COMPOSITIONS LES COMPRENANT ET LEURS UTILISATIONS

  摘要：

  The invention provides crystalline forms of solvates of tryptophan derivatives of compound (1), compositions comprising them, processes for their preparations and methods of use thereof.

  公开号：

  WO2021240333A1
• 作为产物：
  描述：

  H-D-Trp-Aib-OH*HCl 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 以76.9%的产率得到D-Trp-Aib
  参考文献：
  名称：

  [EN] NOVEL POLYMORPH FORM OF ( R)-2-[2-AMINO-3-(INDOL-3-YL)PROPIONYLAMINO]-2-METHYLPROPIONIC ACID AND USES THEREOF
  [FR] NOUVELLE FORME POLYMORPHE D'ACIDE (R)-2-[2-AMINO-3-(INDOL-3-YL)PROPIONYLAMINO]-2-MÉTHYLPROPIONIQUE ET UTILISATIONS ASSOCIÉES

  摘要：

  本发明涉及一种新的多晶形式化合物(R)-2-[2-氨基-3-(吲哚-3-基)丙酰胺基]-2-甲基丙酸，一种制备该化合物新的多晶形式的方法，以及用于制备该化合物的其他多晶形式的用途。本发明还涉及包含该化合物新的多晶形式和药用载体或赋形剂的组合物。

  公开号：

  WO2021059142A1

文献信息

• Bioinformatic and experimental evidence for suicidal and catalytic plant THI4s
  作者：Jaya Joshi、Guillaume A.W. Beaudoin、Jenelle A. Patterson、Jorge D. García-García、Catherine E. Belisle、Lan-Yen Chang、Lei Li、Owen Duncan、A. Harvey Millar、Andrew D. Hanson

  DOI：10.1042/bcj20200297

  日期：2020.6.12

  Like fungi and some prokaryotes, plants use a thiazole synthase (THI4) to make the thiazole precursor of thiamin. Fungal THI4s are suicide enzymes that destroy an essential active-site Cys residue to obtain the sulfur atom needed for thiazole formation. In contrast, certain prokaryotic THI4s have no active-site Cys, use sulfide as sulfur donor, and are truly catalytic. The presence of a conserved active-site Cys in plant THI4s and other indirect evidence implies that they are suicidal. To confirm this, we complemented the Arabidopsistz-1 mutant, which lacks THI4 activity, with a His-tagged Arabidopsis THI4 construct. LC–MS analysis of tryptic peptides of the THI4 extracted from leaves showed that the active-site Cys was predominantly in desulfurated form, consistent with THI4 having a suicide mechanism in planta. Unexpectedly, transcriptome data mining and deep proteome profiling showed that barley, wheat, and oat have both a widely expressed canonical THI4 with an active-site Cys, and a THI4-like paralog (non-Cys THI4) that has no active-site Cys and is the major type of THI4 in developing grains. Transcriptomic evidence also indicated that barley, wheat, and oat grains synthesize thiamin de novo, implying that their non-Cys THI4s synthesize thiazole. Structure modeling supported this inference, as did demonstration that non-Cys THI4s have significant capacity to complement thiazole auxotrophy in Escherichia coli. There is thus a prima facie case that non-Cys cereal THI4s, like their prokaryotic counterparts, are catalytic thiazole synthases. Bioenergetic calculations show that, relative to suicide THI4s, such enzymes could save substantial energy during the grain-filling period.

  与真菌和某些原核生物一样，植物也使用噻唑合成酶（THI4）来制造硫胺素的噻唑前体。真菌的 THI4 是一种自杀式酶，它会破坏活性位点的一个重要 Cys 残基，以获得噻唑形成所需的硫原子。相比之下，某些原核生物的 THI4 没有活性位点 Cys，使用硫化物作为硫供体，具有真正的催化作用。植物 THI4s 中存在一个保守的活性位点 Cys 以及其他间接证据暗示它们是自杀性的。为了证实这一点，我们用 His 标记的拟南芥 THI4 构建体补充了缺乏 THI4 活性的拟南芥 z-1 突变体。对从叶片中提取的 THI4 的胰蛋白酶肽进行的 LC-MS 分析表明，活性位点 Cys 主要以脱硫形式存在，这与 THI4 在植物体内的自杀机制一致。意想不到的是，转录组数据挖掘和深度蛋白质组分析表明，大麦、小麦和燕麦既有广泛表达的带有活性位点 Cys 的典型 THI4，也有类似 THI4 的旁系亲属（非 Cys THI4），后者没有活性位点 Cys，是发育中谷物中的主要 THI4 类型。转录组证据还表明，大麦、小麦和燕麦谷粒会从头合成硫胺素，这意味着它们的非 Cys THI4s 会合成噻唑。结构建模支持这一推论，而且在大肠杆菌中，非 Cys THI4s 也具有显著的补充噻唑辅助营养的能力。因此，有初步证据表明，非胱氨酸谷物 THI4s 与原核对应物一样，是催化噻唑合成酶。生物能计算显示，与自杀式 THI4s 相比，这种酶在谷物灌浆期间可节省大量能量。
• Dipeptide analogs for treating conditions associated with amyloid fibril formation
  申请人：Ramot at Tel-Aviv University Ltd.

  公开号：US09630989B2

  公开（公告）日：2017-04-25

  Dipeptide analogs comprising a tryptophan (Trp) moiety coupled to a beta-sheet breaker moiety derived from alpha-aminoisobutyric acid (Aib) are disclosed. The dipeptide analogs exhibit an improved performance in inhibiting amyloid fibril formation, as compared to previously described dipeptides. Compositions containing the dipetide analogs and uses thereof in treating amyloid-associated diseases and disorders are also disclosed.

  本发明揭示了一种包含色氨酸（Trp）基团与源自α-氨基异丁酸（Aib）的β-折叠片断破坏基团偶联的二肽类似物。与先前描述的二肽相比，这些二肽类似物在抑制淀粉样蛋白纤维形成方面表现出更好的性能。本发明还揭示了含有这些二肽类似物的组合物以及它们在治疗淀粉样相关疾病和疾病方面的用途。
• Multiple Actions of H₂S-Releasing Peptides in Human β-Amyloid Expressing <i>C. elegans</i>
  作者：Rafat Ali、Rohil Hameed、Divya Chauhan、Shantanu Sen、Muhammad Wahajuddin、Aamir Nazir、Sandeep Verma

  DOI：10.1021/acschemneuro.2c00402

  日期：2022.12.7
• INDOLE COMPOUNDS FOR USE IN NEURORESTORATION
  申请人：Galimedix Therapeutics, Inc.

  公开号：US20220193035A1

  公开（公告）日：2022-06-23

  Provided herein are methods of use of indole derivative compounds for reversal of amyloid β toxicity in amyloid β-associated diseases.
• NOVEL POLYMORPH FORM OF (R)-2-[2-AMINO-3-(INDOL-3-YL)PROPIONYLAMINO]-2-METHYLPROPIONIC ACID AND USES THEREOF
  申请人：Galimedix Therapeutics Inc.

  公开号：US20220389056A1

  公开（公告）日：2022-12-08

  This intention relates to a novel polymorph form of compound (R)-2-[2-amino-3-(indol-3-yl)propionylamino]-2-methylpropionic acid, a process for making the novel polymorph form of the compound, and uses thereof for making other polymorph forms of the compound. The invention further relates to composition comprising novel polymorph form of the compound and a pharmaceutically acceptable carrier or excipient.