H₂N-Arg(Pbf)-Gly-Asp(O^tBu)-O^tBu | 1314357-54-4

• 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: H₂N-Arg(Pbf)-Gly-Asp(O^tBu)-O^tBu
• 英文别名: H-Arg(Pbf)-Gly-Asp(OtBu)-OtBu；ditert-butyl (2S)-2-[[2-[[(2S)-2-amino-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]pentanoyl]amino]acetyl]amino]butanedioate
• CAS: 1314357-54-4
• 化学式: C₃₃H₅₄N₆O₉S
• 分子量: 710.893
• InChiKey: JNCQCKSITVSROW-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  49
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  239
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  H₂N-Arg(Pbf)-Gly-Asp(O^tBu)-O^tBu 在 三异丙基硅烷 、 水 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.25h， 生成
  参考文献：
  名称：

  Synthesis and anticancer properties of RGD peptides conjugated to nitric oxide releasing functional groups and abiraterone

  摘要：

  A series of analogues of the integrin binding aspartic acid-glycine-arginine (RGD) peptide sequence were synthesised conjugated to nitric oxide (NO) donating functional groups. Also the cytotoxicity of abiraterone, a prostate cancer drug, was explored when it was conjugated in three part constructs to RGD sequences and NO releasing heterocycles. In general the analogues showed integrin binding affinity comparable to RGD reference compounds, and all released NO by the Griess test assay. Two analogues exhibited significant cytotoxic effects against PO and MCF7 cell lines. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2014.09.004
• 作为产物：
  描述：

  Z-L-天冬氨酸叔丁酯叔丁酯 在 哌啶 、 palladium 10% on activated carbon 、 甲酸铵 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 53.5h， 生成 H₂N-Arg(Pbf)-Gly-Asp(O^tBu)-O^tBu
  参考文献：
  名称：

  Synthesis and anticancer properties of RGD peptides conjugated to nitric oxide releasing functional groups and abiraterone

  摘要：

  A series of analogues of the integrin binding aspartic acid-glycine-arginine (RGD) peptide sequence were synthesised conjugated to nitric oxide (NO) donating functional groups. Also the cytotoxicity of abiraterone, a prostate cancer drug, was explored when it was conjugated in three part constructs to RGD sequences and NO releasing heterocycles. In general the analogues showed integrin binding affinity comparable to RGD reference compounds, and all released NO by the Griess test assay. Two analogues exhibited significant cytotoxic effects against PO and MCF7 cell lines. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2014.09.004

文献信息

• Comparing dendritic and self-assembly strategies to multivalency—RGD peptide–integrin interactions
  作者：Daniel J. Welsh、David K. Smith

  DOI：10.1039/c1ob05241a

  日期：——

  This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC50 of 125 μM (375 μM per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 μM. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.

  本文比较了组织配体阵列以结合整合素的共价和非共价方法。在共价策略中，线性 RGD 肽与第一代和第二代树枝状配体共轭，并使用荧光偏振竞争分析法证明第一代化合物能最有效地结合整合素，EC50 为 125 μM（每个肽单位为 375 μM）。因此，即使浓度高达 1 mM，这种树枝状化合物也比不与整合素结合的单价配体有效得多。不过，第二代化合物的效果明显较差，这表明在这种情况下，多价配体存在一个最佳配体密度。在多价性的非共价方法中，同样的 RGD 肽被疏水的 C12 链功能化，从而产生了一种经证明能够自组装的脂肽。这种脂肽在浓度为 200 ¼M 时就能与整合素有效结合。因此，这些结果表明，在实现配体阵列的多价组织方面，共价（树枝状）和非共价（胶束自组装）方法的效率相当。
• Self-assembled multivalent RGD-peptide arrays – morphological control and integrin binding
  作者：Daniel J. Welsh、Paola Posocco、Sabrina Pricl、David K. Smith

  DOI：10.1039/c3ob00034f

  日期：——

  (CACs). We then probe the multivalent binding of these assemblies to integrin proteins and demonstrate that the spherical micellar assemblies perform well in our solution-phase integrin binding assay as a consequence of self-assembled multivalency, with the CAC switching-on the binding. Conversely, the cylindrical assemblies do not work in this assay. As such, the nanoscale morphology controls the apparent

  我们报告了四种不同的RGD肽衍生物的合成，这些衍生物自发地自组装成纳米级结构。根据通过有机合成编入分子级构造模块的信息，这些化合物组装成不同的纳米级形态。使用多尺度建模可以完全理解此过程，该模型可以提供对细微差异的预测见解，例如化合物是形成球形胶束，杆状圆柱还是管状组件，并预测实验观察到的临界聚集浓度（CAC）。然后，我们探究这些组装体与整联蛋白的多价结合，并证明由于自组装多价，球形胶束组装体在我们的溶液相整联蛋白结合测定中表现良好，使用CAC打开绑定。相反，在此测定中，圆柱形组件不起作用。这样，纳米级形态控制着表现为自组装多价配体阵列的表观能力。
• Synthesis of closo- and nido-carborane derivatives of the KRGD peptide
  作者：Dmitry A. Gruzdev、Alexander V. Vakhrushev、Alexander M. Demin、Maria A. Baryshnikova、Galina L. Levit、Victor P. Krasnov、Valery N. Charushin

  DOI：10.1016/j.jorganchem.2024.123052

  日期：2024.3

  of the peptide containing ‑carborane residues made it possible to obtain a (‑carboranyl) tetrapeptide containing 20 wt.% boron and having high solubility in water (up to 5 mg/mL). In vitro experiments demonstrated the low cytotoxicity of the KRGD peptide containing two ‑carborane residues (CC > 100 μmol/L). The developed synthetic approach to KRGD derivatives containing 18–20 boron atoms per molecule

  RGD 家族的肽作为将各种治疗和诊断基团靶向递送至肿瘤细胞的载体具有重要意义。它们的应用对于实施恶性肿瘤的硼中子捕获疗法（BNCT）特别有用。我们开发了一种获得赖氨酸-精氨酸-甘氨酸-天冬氨酸 (KRGD) 肽衍生物的方法，其中包含与赖氨酸残基连接的两个 - 或 - 碳硼烷片段。研究表明，要获得具有游离官能团的(-碳硼烷基)KRGD肽，最好使用可在弱酸性条件下去除的保护基团。对含有碳硼烷残基的肽进行脱硼，可以获得含有 20 wt.% 硼且在水中具有高溶解度（高达 5 mg/mL）的（碳硼烷基）四肽。体外实验证明含有两个碳硼烷残基的 KRGD 肽具有低细胞毒性 (CC > 100 μmol/L)。所开发的每分子含有 18-20 个硼原子的 KRGD 衍生物的合成方法为 BNCT 的潜在硼输送剂开辟了道路。
• Functionalization of Fe3O4 magnetic nanoparticles with RGD peptide derivatives
  作者：Alexander M. Demin、Alexey Yu. Vigorov、Irina A. Nizova、Mikhail A. Uimin、Nina N. Shchegoleva、Anatoly E. Ermakov、Victor P. Krasnov、Valery N. Charushin

  DOI：10.1016/j.mencom.2013.12.006

  日期：2014.1

  Derivatives of RGD peptide, such as N-omega-Pbf-L-Arg-Gly-L-Asp(OAlk)(2) (Alk = Me or Bu-t), which contain glutaric acid moiety as a linker, were synthesized and immobilized to Fe3O4 magnetic nanoparticles obtained by gas condensation method.
• Synthesis and anticancer properties of RGD peptides conjugated to nitric oxide releasing functional groups and abiraterone
  作者：Andrew Nortcliffe、Ian N. Fleming、Nigel P. Botting、David O'Hagan

  DOI：10.1016/j.tet.2014.09.004

  日期：2014.11

  A series of analogues of the integrin binding aspartic acid-glycine-arginine (RGD) peptide sequence were synthesised conjugated to nitric oxide (NO) donating functional groups. Also the cytotoxicity of abiraterone, a prostate cancer drug, was explored when it was conjugated in three part constructs to RGD sequences and NO releasing heterocycles. In general the analogues showed integrin binding affinity comparable to RGD reference compounds, and all released NO by the Griess test assay. Two analogues exhibited significant cytotoxic effects against PO and MCF7 cell lines. (C) 2014 Published by Elsevier Ltd.