(2R)-2-[[(2R)-2-[[(2R)-2-[(2-naphthalen-2-ylacetyl)amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoic acid

• 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: (2R)-2-[[(2R)-2-[[(2R)-2-[(2-naphthalen-2-ylacetyl)amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoic acid
• 化学式: C₃₉H₃₈N₃O₉P
• 分子量: 723.719
• InChiKey: XHYHCCUSRPNVAU-YAFWASLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  52
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  191
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R)-2-[[(2R)-2-[[(2R)-2-[(2-naphthalen-2-ylacetyl)amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 肼 作用下， 生成 [4-[(2R)-3-hydrazinyl-2-[[(2R)-2-[[(2R)-2-[(2-naphthalen-2-ylacetyl)amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate
  参考文献：
  名称：

  Minimal C-terminal modification boosts peptide self-assembling ability for necroptosis of cancer cells

  摘要：

  对a-d肽进行C-末端修饰可以增强其自组装能力，并在细胞实验中将肽的抗癌活性提高一个数量级。

  DOI：

  10.1039/c6cc02282k

文献信息

• Enzyme-Instructed Assembly and Disassembly Processes for Targeting Downregulation in Cancer Cells
  作者：Zhaoqianqi Feng、Huaimin Wang、Rong Zhou、Jie Li、Bing Xu

  DOI：10.1021/jacs.7b00070

  日期：2017.3.22

  Cancer cells differ from normal cells in both gain of functions (i.e., upregulation) and loss of functions (i.e., downregulation). While it is common to suppress gain of function for chemotherapy, it remains challenging to target downregulation in cancer cells. Here we show the combination of enzyme-instructed assembly and disassembly to target downregulation in cancer cells by designing peptidic precursors

  癌细胞在功能获得（即上调）和功能丧失（即下调）方面与正常细胞不同。虽然抑制化疗功能的获得很常见，但靶向癌细胞的下调仍然具有挑战性。在这里，我们通过设计肽前体作为羧酸酯酶 (CES) 和碱性磷酸酶 (ALP) 的底物，展示了酶指导的组装和分解的组合，以靶向癌细胞中的下调。前体在被 ALP 去磷酸化后变成自组装分子以形成纳米纤丝，但 CES 催化的分子上酯键的裂解导致纳米纤丝的分解。前体选择性抑制下调 CES 的癌细胞（例如 OVSAHO），但对过度表达 CES 的肝细胞（HepG2）无害，而两种细胞系表现出相当的 ALP 活性。这项工作说明了通过靶向癌细胞中的下调（或功能丧失）来开发化疗的潜在方法。
• <scp>d</scp>-Amino Acids Modulate the Cellular Response of Enzymatic-Instructed Supramolecular Nanofibers of Small Peptides
  作者：Junfeng Shi、Xuewen Du、Dan Yuan、Jie Zhou、Ning Zhou、Yibing Huang、Bing Xu

  DOI：10.1021/bm5010355

  日期：2014.10.13

  Peptides made of d-amino acids, as the enantiomer of corresponding l-peptides, are able to resist proteolysis. It is, however, unclear or much less explored whether or how d-amino acids affect the cellular response of supramolecular nanofibers formed by enzyme-triggered self-assembly of d-peptides. In this work, we choose a cell compatible molecule, Nap-l-Phe-l-Phe-l-pTyr (LLL-1P), and systematically replace the l-amino acids in this tripeptidic precursor or its hydrogelator by the corresponding d-amino acid(s). The replacement of even one d-amino acid in this tripeptidic precursor increases its proteolytic resistance. The results of static light scattering and TEM images show the formation of nanostructures upon the addition of alkaline phosphatase, even at concentrations below the minimum gelation concentration (mgc). All these isomers are able to form ordered nanostructures and exhibit different morphologies. According to the cell viability assay on these stereochemical isomers, cells exhibit drastically different responses to the enantiomeric precursors, but almost same responses to the enantiomeric hydrogelators. Furthermore, the different cellular responses of LLL-1P and DDD-1P largely originate from the ecto-phosphatases catalyzed self-assembly of DDD-1 on the surface of cells. Therefore, this report not only illustrates a new way for tailoring the properties of supramolecular assemblies, but also provides new insights to answering the fundamental question of how mammalian cells respond to enzymatic formation of nanoscale supramolecular assemblies (e.g., nanofibers) of d-peptides.
• SYNTHETIC PEPTIDES, ENZYMATIC FORMATION OF PERICELLULAR HYDROGELS/NANOFIBRILS, AND METHODS OF USE
  申请人：BRANDEIS UNIVERSITY

  公开号：US20170037082A1

  公开（公告）日：2017-02-09

  Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester-moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels/nanofibrils form, and screening the collected secretome.
• [EN] SYNTHETIC PEPTIDES, ENZYMATIC FORMATION OF PERICELLULAR HYDROGELS/NANOFIBRILS, AND METHODS OF USE<br/>[FR] PEPTIDES SYNTHÉTIQUES, FORMATION ENZYMATIQUE D'HYDROGELS/NANOFIBRILES PÉRICELLULAIRES, ET PROCÉDÉS D'UTILISATION
  申请人：UNIV BRANDEIS

  公开号：WO2015157535A2

  公开（公告）日：2015-10-15

  Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester- moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels/nanofibrils form, and screening the collected secretome.