3-((((9H-芴-9-基)甲氧基)羰基)氨基)戊二酸 | 247217-28-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 3-((((9H-芴-9-基)甲氧基)羰基)氨基)戊二酸
• 英文名称: 3-(N-fluorenylmethoxycarbonylamino)glutaric acid
• 英文别名: fluorenylmethoxycarbonyl-β³-homoaspartate tert-butyl ester；Fmoc-β³-Asp(tBu)-OH；3-(9H-fluoren-9-ylmethoxycarbonylamino)pentanedioic acid；Fmoc-β-Glu(OH)-OH；3-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)pentanedioic acid
• CAS: 247217-28-3
• 化学式: C₂₀H₁₉NO₆
• 分子量: 369.374
• InChiKey: ZVTDIOCXLUVDEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P330,P362,P403+P233,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  3-((((9H-芴-9-基)甲氧基)羰基)氨基)戊二酸 在 哌啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 生成 homo-β-(L,D)-aspartyl-L-phenylalanine methyl ester
  参考文献：
  名称：

  Synthesis and conformation of dipeptide taste ligands containinghomo-β-amino acid residues

  摘要：

  The synthesis and conformational properties of a series of dipeptide taste ligands, differing from the commercial sweetener aspartame by the presence of a methylene group between the C-alpha and the C' carbon atoms (as in homo-beta-residues) in either the L-Asp or the L-Phe residues, are described. Homo-beta-residues such as homo-beta-aspartic acid, homo-beta-phenylglycine and homo-beta-phenylalanine, obtained by homologation of the corresponding proteinogenic alpha-amino acids, have been used in the solution peptide synthesis of the following aspartame analogues in protected and unprotected forms: NH2-homo-beta-(L or D)-Asp-L-Phe-OMe, NH2-L-Asp-homo-beta-L-Phg-OMe and NH2-L-Asp-homo-beta-L-Phe-OMe. Lengthening of the peptide skeleton at the L-Asp site results in a drastic loss of sweetness with the production of tasteless compounds; on the other hand, lengthening of the skeleton at the C-terminal L-Phe site partially mantains the sweet taste in both NH2-L-Asp-homo-beta-L-Phe-OMe and NH2-L-Asp-homo-beta-L-Phg-OMe. The solution conformation of the synthesized dipeptide taste ligands was investigated by NMR and circular dichroism techniques. The analysis of NMR data combined with restrained molecular dynamics calculations shows that all peptides are fairly flexible and they do not assume a preferred conformation in DMSO and methanol. The peptides containing homo-beta-L-Phe and homo-beta-L-Phg do adopt a discrete number of conformations among which mainly extended and 'L-shaped' conformation are represented. The circular dichroism spectra are consistent with the NMR results, indicating a significant flexibility for these compounds. Copyright (C) 1999 John Wiley & Sons, Ltd.

  DOI：

  10.1002/(sici)1099-1395(199907)12:7<577::aid-poc159>3.0.co;2-f
• 作为产物：
  描述：

  3-(N-fluorenylmethoxycarbonylamino)-4-cyano benzylbutyrate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 以71%的产率得到3-((((9H-芴-9-基)甲氧基)羰基)氨基)戊二酸
  参考文献：
  名称：

  Synthesis and conformation of dipeptide taste ligands containinghomo-β-amino acid residues

  摘要：

  The synthesis and conformational properties of a series of dipeptide taste ligands, differing from the commercial sweetener aspartame by the presence of a methylene group between the C-alpha and the C' carbon atoms (as in homo-beta-residues) in either the L-Asp or the L-Phe residues, are described. Homo-beta-residues such as homo-beta-aspartic acid, homo-beta-phenylglycine and homo-beta-phenylalanine, obtained by homologation of the corresponding proteinogenic alpha-amino acids, have been used in the solution peptide synthesis of the following aspartame analogues in protected and unprotected forms: NH2-homo-beta-(L or D)-Asp-L-Phe-OMe, NH2-L-Asp-homo-beta-L-Phg-OMe and NH2-L-Asp-homo-beta-L-Phe-OMe. Lengthening of the peptide skeleton at the L-Asp site results in a drastic loss of sweetness with the production of tasteless compounds; on the other hand, lengthening of the skeleton at the C-terminal L-Phe site partially mantains the sweet taste in both NH2-L-Asp-homo-beta-L-Phe-OMe and NH2-L-Asp-homo-beta-L-Phg-OMe. The solution conformation of the synthesized dipeptide taste ligands was investigated by NMR and circular dichroism techniques. The analysis of NMR data combined with restrained molecular dynamics calculations shows that all peptides are fairly flexible and they do not assume a preferred conformation in DMSO and methanol. The peptides containing homo-beta-L-Phe and homo-beta-L-Phg do adopt a discrete number of conformations among which mainly extended and 'L-shaped' conformation are represented. The circular dichroism spectra are consistent with the NMR results, indicating a significant flexibility for these compounds. Copyright (C) 1999 John Wiley & Sons, Ltd.

  DOI：

  10.1002/(sici)1099-1395(199907)12:7<577::aid-poc159>3.0.co;2-f

文献信息

• Bifunctional cytotoxic agents
  申请人：Pfizer Inc.

  公开号：US10086085B2

  公开（公告）日：2018-10-02

  Cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, antibody drug conjugates comprising such dimers, and to methods for using the same to treat cancer and other conditions.

  细胞毒性二聚体，包括基于CBI和/或基于CPI的亚单位，抗体药物偶联物包括这样的二聚体，以及使用同一方法治疗癌症和其他疾病。
• BIFUNCTIONAL CYTOTOXIC AGENTS
  申请人：Pfizer Inc.

  公开号：US20150209445A1

  公开（公告）日：2015-07-30

  Cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, antibody drug conjugates comprising such dimers, and to methods for using the same to treat cancer and other conditions.

  细胞毒性二聚体包括基于CBI和/或CPI的亚单位，包括这种二聚体的抗体药物结合物，以及使用它们治疗癌症和其他疾病的方法。
• Creating Diverse Target-Binding Surfaces on FKBP12: Synthesis and Evaluation of a Rapamycin Analogue Library
  作者：Xianghong Wu、Lisheng Wang、Yaohua Han、Nicholas Regan、Pui-Kai Li、Miguel A. Villalona、Xiche Hu、Roger Briesewitz、Dehua Pei

  DOI：10.1021/co200057n

  日期：2011.9.12

  library of bifunctional cyclic peptides as FK506 and rapamycin analogues, which were referred to as “rapalogs”. Each rapalog consists of a common FKBP-binding moiety and a variable effector domain. The rapalogs were tested for binding to FKBP12 by a fluorescence polarization competition assay. Our results show that FKBP12 binds to most of the rapalogs with high affinity (KI values in the nanomolar to

  FK506和雷帕霉素是具有独特作用方式的免疫抑制药物。在与它们的蛋白质靶标结合之前，这些药物与内源性伴侣FK506结合蛋白12（FKBP12）形成复合物。所得的复合FK506-FKBP和雷帕霉素-FKBP结合表面分别以高亲和力和特异性识别钙调神经磷酸酶和mTOR的相对平坦的靶表面。为了测试这种作用方式是否可以普遍用于抑制其他蛋白质靶标，特别是那些难以被常规小分子抑制的蛋白质靶标，我们开发了一种平行合成方法来生成具有200个成员的双功能环状肽库，如FK506和雷帕霉素类似物，被称为“ rapalogs”。每个rapalog由共同的FKBP结合部分和可变的效应子结构域组成。通过荧光偏振竞争测定法测试了rapalog与FKBP12的结合。我们的结果表明，FKBP12以高亲和力与大多数rapalog结合（K I值在纳摩尔到低微摩尔范围内），创建了一个大的复合表面库，可潜在地识别大分子靶标，例如蛋白质。
• Method for preparing a ligand presenting assembly (LPA), an LPA and uses thereof
  申请人：Statens Serum Institut

  公开号：US20040086949A1

  公开（公告）日：2004-05-06

  The present invention relates to a method for preparing a ligand presenting assembly (LPA), an LPA, an immunological composition and a vaccine. The invention further relates to a method for generating antibodies, a kit for use in diagnosis and use of an LPA for preparing a pharmaceutical composition.

  本发明涉及一种制备配体呈现组装体（LPA）、LPA、免疫组合物和疫苗的方法。该发明还涉及一种产生抗体的方法，用于诊断的试剂盒以及使用LPA制备药物组合物的方法。
• 18F-FP-PEG2-β-Glu-RGD2: A Symmetric Integrin αvβ3-Targeting Radiotracer for Tumor PET Imaging
  作者：Kongzhen Hu、Xiaolan Tang、Ganghua Tang、Shaobo Yao、Baoguo Yao、Hongliang Wang、Dahong Nie、Xiang Liang、Caihua Tang、Shanzhen He

  DOI：10.1371/journal.pone.0138675

  日期：——

  Radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive determination of integrin αvβ3 expression in tumors. In this study, we performed radiosynthesis and biological evaluation of a new 18F-labeled RGD homodimeric peptide with one 8-amino-3,6-dioxaoctanoic acid (PEG2) linker on the glutamate β-amino group (18F-FP-PEG2-β-Glu-RGD2) as a symmetric PET tracer for tumor imaging. Biodistribution studies showed that radioactivity of 18F-FP-PEG2-β-Glu-RGD2 was rapidly cleared from blood by predominately renal excretion. MicroPET-CT imaging with 18F-FP-PEG2-β-Glu-RGD2 revealed high tumor contrast and low background in A549 human lung adenocarcinoma-bearing mouse models, PC-3 prostate cancer-bearing mouse models, and orthotopic transplanted C6 brain glioma models. 18F-FP-PEG2-β-Glu-RGD2 exhibited good stability in vitro and in vivo. The results suggest that this tracer is a potential PET tracer for tumor imaging.

  放射性标记的环精氨酸-甘氨酸-天冬氨酸（RGD）肽可用于无创检测肿瘤中整合素αvβ3的表达。在这项研究中，我们对一种新的 18F 标记 RGD 同源二聚体肽进行了放射合成和生物学评估，该肽在谷氨酸 β-氨基上有一个 8-氨基-3,6-二氧杂辛酸（PEG2）连接基（18F-FP-PEG2-β-Glu-RGD2），是一种用于肿瘤成像的对称 PET 示踪剂。生物分布研究表明，18F-FP-PEG2-β-Glu-RGD2 的放射性会迅速从血液中清除，主要通过肾脏排泄。在 A549 人肺腺癌小鼠模型、PC-3 前列腺癌小鼠模型和正位移植 C6 脑胶质瘤模型中，18F-FP-PEG2-β-Glu-RGD2 的 MicroPET-CT 成像显示肿瘤对比度高，背景低。18F-FP-PEG2-β-Glu-RGD2 在体外和体内均表现出良好的稳定性。结果表明，该示踪剂是一种潜在的肿瘤成像 PET 示踪剂。