N-[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]-6-[4-[4-[[(2R,3R,4S,5R,6R)-3,4,5-tris[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxy]-6-[(2S,3S,4R,5R)-3,4-bis[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxy]-2,5-bis[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxymethyl]oxolan-2-yl]oxyoxan-2-yl]methoxy]butyl]triazol-1-yl]hexanamide | 1345721-28-9

• 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: N-[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]-6-[4-[4-[[(2R,3R,4S,5R,6R)-3,4,5-tris[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxy]-6-[(2S,3S,4R,5R)-3,4-bis[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxy]-2,5-bis[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxymethyl]oxolan-2-yl]oxyoxan-2-yl]methoxy]butyl]triazol-1-yl]hexanamide
• CAS: 1345721-28-9
• 化学式: C₁₃₂H₂₂₂N₄₀O₃₅
• 分子量: 2929.46
• InChiKey: IEXVATQCBPEAIM-BWRYYPERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -9.1
• 重原子数：
  207
• 可旋转键数：
  125
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  1090
• 氢给体数：
  24
• 氢受体数：
  51

反应信息

• 作为产物：
  描述：

  N-(1-amino-3-hydroxy-1-oxopropan-2-yl)-6-azidohexanamide 、 octa-O-(5-hexyn-1-yl)-β-D-fructofuranosyl-α-D-glucopyranoside 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以15%的产率得到N-[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]-6-[4-[4-[[(2R,3R,4S,5R,6R)-3,4,5-tris[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxy]-6-[(2S,3S,4R,5R)-3,4-bis[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxy]-2,5-bis[4-[1-[6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]triazol-4-yl]butoxymethyl]oxolan-2-yl]oxyoxan-2-yl]methoxy]butyl]triazol-1-yl]hexanamide
  参考文献：
  名称：

  A sucrose-derived scaffold for multimerization of bioactive peptides

  摘要：

  A spherical molecular scaffold bearing eight terminal alkyne groups was synthesized in one step from sucrose. One or more copies of a tetrapeptide azide, either N-3(CH2)(5)(C=O)-His-DPhe-Arg-Trp-NH2 (MSH4) or N-3(CH2)(5)(C=O)-Trp-Met-Asp-Phe-NH2 (CCK4), were attached to the scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Competitive binding assays using Eu-labeled probes based on the superpotent ligands Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (NDP-alpha-MSH) and Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 (CCK8) were used to study the interactions of monovalent and multivalent MSH4 and CCK4 constructs with Hek293 cells engineered to overexpress MC4R and CCK2R. All of the monovalent and multivalent MSH4 constructs exhibited binding comparable to that of the parental ligand, suggesting that either the ligand spacing was inappropriate for multivalent binding, or MSH4 is too weak a binder for a second 'anchoring' binding event to occur before the monovalently-bound construct is released from the cell surface. In contrast with this behavior, monovalent CCK4 constructs were significantly less potent than the parental ligand, while multivalent CCK4 constructs were as or more potent than the parental ligand. These results are suggestive of multivalent binding, which may be due to increased residence times for monovalently bound CCK4 constructs on the cell surface relative to MSH4 constructs, the greater residence time being necessary for the establishment of multivalent binding. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.053

文献信息

• A sucrose-derived scaffold for multimerization of bioactive peptides
  作者：Venkataramanarao Rao、Ramesh Alleti、Liping Xu、Narges K. Tafreshi、David L. Morse、Robert J. Gillies、Eugene A. Mash

  DOI：10.1016/j.bmc.2011.08.053

  日期：2011.11

  A spherical molecular scaffold bearing eight terminal alkyne groups was synthesized in one step from sucrose. One or more copies of a tetrapeptide azide, either N-3(CH2)(5)(C=O)-His-DPhe-Arg-Trp-NH2 (MSH4) or N-3(CH2)(5)(C=O)-Trp-Met-Asp-Phe-NH2 (CCK4), were attached to the scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Competitive binding assays using Eu-labeled probes based on the superpotent ligands Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (NDP-alpha-MSH) and Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 (CCK8) were used to study the interactions of monovalent and multivalent MSH4 and CCK4 constructs with Hek293 cells engineered to overexpress MC4R and CCK2R. All of the monovalent and multivalent MSH4 constructs exhibited binding comparable to that of the parental ligand, suggesting that either the ligand spacing was inappropriate for multivalent binding, or MSH4 is too weak a binder for a second 'anchoring' binding event to occur before the monovalently-bound construct is released from the cell surface. In contrast with this behavior, monovalent CCK4 constructs were significantly less potent than the parental ligand, while multivalent CCK4 constructs were as or more potent than the parental ligand. These results are suggestive of multivalent binding, which may be due to increased residence times for monovalently bound CCK4 constructs on the cell surface relative to MSH4 constructs, the greater residence time being necessary for the establishment of multivalent binding. (C) 2011 Elsevier Ltd. All rights reserved.