Fmoc-D-His(Trt)-OH

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: Fmoc-D-His(Trt)-OH
• 英文别名: (2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(3-tritylimidazol-4-yl)propanoic acid
• 化学式: C₄₀H₃₃N₃O₄
• 分子量: 619.72
• InChiKey: LCDUPKDPUSBXAY-DIPNUNPCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  咖啡酸 、 Fmoc-D-脯氨酸 、 Fmoc-D-His(Trt)-OH 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Antioxidant activity of caffeoyl-prolyl-histidine amide and its effects on PDGF-induced proliferation of vascular smooth muscle cells

  摘要：

  Caffeic acid (CA) is one of the antioxidants found in plants, which protects vascular cells against vascular injuries from oxidative stress. In our previous study, caffeoyl-prolyl-histidine amide (CA-L-Pro-L-His-NH2; CA-PH; a CA derivative) was synthesized, which exhibited a strong antioxidant activity with sufficient stability. In this study, we investigated the role of CA-PH in vascular smooth muscle cells (VSMCs) and confirmed the enhanced antioxidant activity of CA-PH compared with that of CA. In in vitro tube assays, CA-PH showed a higher free-radical-scavenging activity and lipid-peroxidation-inhibition activity than those of CA. In VSMCs, CA-PH significantly reduced hydrogen peroxide-induced ROS generation and increased the expression of heme oxygenase-1. Moreover, CA-PH effectively inhibited the platelet-derived growth factor-induced cellular proliferation of VSMCs, which was confirmed by a decrease in the expression of the proliferating cell nuclear antigen and the phosphorylation of Akt.

  DOI：

  10.1007/s00726-014-1834-8

文献信息

• Systemic Antibacterial Activity of Novel Synthetic Cyclic Peptides
  作者：Véronique Dartois、Jorge Sanchez-Quesada、Edelmira Cabezas、Ellen Chi、Chad Dubbelde、Carrie Dunn、Juan Granja、Colleen Gritzen、Dana Weinberger、M. Reza Ghadiri、Thomas R. Parr

  DOI：10.1128/aac.49.8.3302-3310.2005

  日期：2005.8

  Cyclic peptides with an even number of alternatingd,l-α-amino acid residues are known to self-assemble into organic nanotubes. Such peptides previously have been shown to be stable upon protease treatment, membrane active, and bactericidal and to exert antimicrobial activity againstStaphylococcus aureusand other gram-positive bacteria. The present report describes the in vitro and in vivo pharmacology of selected members of this cyclic peptide family. The intravenous (i.v.) efficacy of six compounds with MICs of less than 12 μg/ml was tested in peritonitis and neutropenic-mouse thigh infection models. Four of the six peptides were efficacious in vivo, with 50% effective doses in the peritonitis model ranging between 4.0 and 6.7 mg/kg against methicillin-sensitiveS. aureus(MSSA). In the thigh infection model, the four peptides reduced the bacterial load 2.1 to 3.0 log units following administration of an 8-mg/kg i.v. dose. Activity against methicillin-resistantS. aureuswas similar to MSSA. The murine pharmacokinetic profile of each compound was determined following i.v. bolus injection. Interestingly, those compounds with poor efficacy in vivo displayed a significantly lower maximum concentration of the drug in serum and a higher volume of distribution at steady state than compounds with good therapeutic properties.S. aureuswas unable to easily develop spontaneous resistance upon prolonged exposure to the peptides at sublethal concentrations, in agreement with the proposed interaction with multiple components of the bacterial membrane canopy. Although additional structure-activity relationship studies are required to improve the therapeutic window of this class of antimicrobial peptides, our results suggest that these amphipathic cyclicd,l-α-peptides have potential for systemic administration and treatment of otherwise antibiotic-resistant infections.

  摘要已知具有偶数个交替的 d,l-α-氨基酸残基的环肽可以自组装成有机纳米管。以前的研究表明，这种肽在蛋白酶处理后具有稳定性、膜活性和杀菌性，并对金黄色葡萄球菌和其他革兰氏阳性细菌具有抗菌活性。本报告介绍了该环肽家族部分成员的体外和体内药理学。在腹膜炎和嗜中性粒细胞小鼠大腿感染模型中，对 MIC 小于 12 μg/ml 的六种化合物进行了静脉注射药效测试。在腹膜炎模型中，六种肽中的四种对甲氧西林敏感金黄色葡萄球菌（MSSA）的50%有效剂量为4.0至6.7毫克/千克。在大腿感染模型中，静脉注射 8 毫克/千克的剂量后，四种肽能使细菌量减少 2.1 至 3.0 log 单位。对耐甲氧西林金黄色葡萄球菌的活性与 MSSA 相似。在静脉注射后，测定了每种化合物的小鼠药代动力学特征。有趣的是，与疗效好的化合物相比，体内疗效差的化合物在血清中的最大药物浓度明显较低，稳态分布容积也较高。金黄色葡萄球菌在长期接触亚致死浓度的肽后不易产生自发抗药性，这与所提出的与细菌膜顶盖的多种成分相互作用是一致的。虽然还需要进行更多的结构-活性关系研究来改善这类抗菌肽的治疗窗口，但我们的研究结果表明，这些两性环d,l-α-肽具有全身给药和治疗抗生素耐药性感染的潜力。
• Solid-Phase Synthesis and Biological Evaluation of a Pepticinnamin E Library
  作者：Michael Thutewohl、Lars Kissau、Boriana Popkirova、Ionna-Maria Karaguni、Thorsten Nowak、Michael Bate、Jürgen Kuhlmann、Oliver Müller、Herbert Waldmann

  DOI：10.1002/1521-3773(20021004)41:19<3616::aid-anie3616>3.0.co;2-f

  日期：2002.10.4