4-iodo-L-phenylalanine

• 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: 4-iodo-L-phenylalanine
• 英文别名: L-p-iodophenylalanine；(2S)-2-azaniumyl-3-(4-iodophenyl)propanoate
• 化学式: C₉H₁₀INO₂
• 分子量: 291.088
• InChiKey: PZNQZSRPDOEBMS-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-iodo-L-phenylalanine 在 盐酸 、 硫酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 27.5h， 生成 (S)-ethyl 2-hydroxy-3-(4-iodophenyl)propanoate
  参考文献：
  名称：

  Identification of the First PPARα/γ Dual Agonist Able To Bind to Canonical and Alternative Sites of PPARγ and To Inhibit Its Cdk5-Mediated Phosphorylation

  摘要：

  A new series of derivatives of the PPAR alpha/gamma dual agonist 1 allowed us to identify the ligand (S)-6 as a potent partial agonist of both PPAR alpha and gamma subtypes. X-ray studies in PPAR gamma revealed two different binding modes of (S)-6 to the canonical site. However, (S)-6 was also able to bind an alternative site as demonstrated by transactivation assay in the presence of a canonical PPAR gamma antagonist and supported from docking experiments. This compound did not activate the PPAR gamma-dependent program of adipocyte differentiation inducing a very less severe lipid accumulation compared to rosiglitazone but increased the insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Finally, (S)-6 inhibited the Cdk5-mediated phosphorylation of PPAR gamma at serine 273 that is currently considered the mechanism by which some PPAR gamma partial agonists exert antidiabetic effects similar to thiazolidinediones, without showing their typical side effects. This is the first PPAR alpha/gamma dual agonist reported to show this inhibitory effect representing the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.

  DOI：

  10.1021/acs.jmedchem.8b00835
• 作为产物：
  描述：

  L-苯丙氨酸 在 硫酸 、 碘 、 溶剂黄146 、 sodium iodide 作用下， 反应 21.0h， 以87%的产率得到4-iodo-L-phenylalanine
  参考文献：
  名称：

  Synthesis of Six Phenylalanine Derivatives and their Cell Toxicity Effect on Human Colon Cancer Cell Line HT-29

  摘要：

  一些苯丙氨酸（Phe）衍生物在药理学中具有重要作用，并可能用作药物原料和药物中间体。为了解苯丙氨酸衍生物的细胞毒性，我们合成了L-4-溴苯丙氨酸（Brp）、L-4-碘苯丙氨酸（Ip）、L-4-硝基苯丙氨酸（Np）、L-4-磺酸苯丙氨酸（Sp）、L-4-磷酸苯丙氨酸（Pp）和L-4-氨基苯丙氨酸（Np）。我们通过质谱（MS）、红外光谱（IR）或氢-1核磁共振谱（1H-NMR）以及高效液相色谱（HPLC）检测这些产品的正确性，MTT法和Hoechst33258染色检测它们对人结肠癌HT-29细胞的细胞毒性效应。结果显示，这些产品是正确的，Pp、Ip、Sp和Np的细胞毒性对HT-29细胞基本无影响。此外，Pp、Ip和Sp诱导细胞凋亡，其他三种苯丙氨酸衍生物既不诱导凋亡也不诱导坏死。

  DOI：

  10.2174/1570180812666141206001604

文献信息

• Inhibitors of cathepsin S
  申请人：IRM LLC

  公开号：US20040198780A1

  公开（公告）日：2004-10-07

  The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme (e.g., cathespin K). The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

  本发明提供了用于选择性抑制蛋白酶S的化合物、组合物和方法。在一个优选方面，当至少存在另一种蛋白酶同工酶（例如，蛋白酶K）时，选择性地抑制蛋白酶S。本发明还提供了通过选择性抑制蛋白酶S来治疗受试者疾病状态的方法。
• A Bifunctional Amino Acid Enables Both Covalent Chemical Capture and Isolation of in Vivo Protein-Protein Interactions
  作者：Cassandra M. Joiner、Meghan E. Breen、James Clayton、Anna K. Mapp

  DOI：10.1002/cbic.201600578

  日期：2017.1.17

  Using the bifunctional unnatural amino acid, BPKyne, we have developed a strategy to capture and directly label transient protein–protein interactions (PPIs) in their native environment. Click chemical functionalization post‐crosslinking with a biotin–azide probe enabled the isolation of transcriptional protein complexes from yeast cells. This amino acid will expand the toolbox for the discovery of

  使用双功能非天然氨基酸BPKyne，我们开发了一种策略，可以在其天然环境中捕获并直接标记瞬时蛋白-蛋白相互作用（PPI）。单击化学功能后与生物素-叠氮化物探针进行交联，可以从酵母细胞中分离出转录蛋白复合物。这种氨基酸将扩大在活细胞中发现新PPI的工具箱。
• Electron‐deficient p‐benzoyl‐ <scp>l</scp> ‐phenylalanine derivatives increase covalent chemical capture yields for protein–protein interactions
  作者：Cassandra M. Joiner、Meghan E. Breen、Anna K. Mapp

  DOI：10.1002/pro.3621

  日期：2019.6

  The photoactivatable amino acid p‐benzoyl‐l‐phenylalanine (pBpa) has been used for the covalent capture of protein–protein interactions (PPIs) in vitro and in living cells. However, this technique often suffers from poor photocrosslinking yields due to the low reactivity of the active species. Here we demonstrate that the incorporation of halogenated pBpa analogs into proteins leads to increased crosslinking

  可光活化的氨基酸对苯甲酰基-1-苯丙氨酸（pBpa）已用于在体外和活细胞中共价捕获蛋白质-蛋白质相互作用（PPI）。然而，由于活性物质的低反应性，该技术经常遭受不良的光交联产率。在这里，我们证明了将卤化的pBpa类似物掺入蛋白质中可以提高蛋白质与蛋白质相互作用的交联产率。可以将类似物掺入活酵母中，并在辐射下捕获内源性PPI。卤化的pBpa将扩展可捕获的PPI的范围，并扩展用于在其本机环境中映射PPI的工具箱。
• [EN] AZASULFURYLPEPTIDE-BASED CD36 MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS CD36 À BASE D'AZASULFURYLPEPTIDES ET UTILISATIONS DE CEUX-CI
  申请人：RSEM LTD PARTNERSHIP

  公开号：WO2016029324A1

  公开（公告）日：2016-03-03

  Novel azasulfuryl-containing peptidomimetics capable of inhibiting CD36 activity are disclosed. Use of these azasulfuryl-containing peptidomimetics for the treatment of CD36-related diseases, disorders or conditions, including TLR2-mediated inflammatory disease, disorder or condition, and methods of obtaining such azasulfuryl-containing peptidomimetics, are also disclosed.

  揭示了能够抑制CD36活性的新型含氮硫酰基的肽类模拟物。还揭示了利用这些含氮硫酰基的肽类模拟物治疗与CD36相关的疾病、紊乱或状况，包括TLR2介导的炎症性疾病、紊乱或状况的用途，以及获取这种含氮硫酰基的肽类模拟物的方法。
• Substituted ureas as cell adhesion inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06353099B1

  公开（公告）日：2002-03-05

  Compounds of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes.

  公式I的化合物是VLA-4和/或α4β7的拮抗剂，因此在抑制或预防细胞粘附和细胞粘附介导的病理过程中非常有用。这些化合物可以制成药物组合物，并适用于治疗艾滋病相关痴呆、过敏性结膜炎、过敏性鼻炎、阿尔茨海默病、哮喘、动脉粥样硬化、自体骨髓移植、某些类型的毒性和免疫性肾炎、接触性皮肤过敏、炎症性肠病包括溃疡性结肠炎和克罗恩病、炎症性肺部疾病、病毒感染的炎症后遗症、脑膜炎、多发性硬化症、多发性骨髓瘤、心肌炎、器官移植、牛皮癣、肺纤维化、再狭窄、视网膜炎、类风湿性关节炎、败血性关节炎、中风、肿瘤转移、葡萄膜炎和I型糖尿病的治疗。