(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-[4-[[1-(carboxymethyl)triazol-4-yl]methoxy]phenyl]ethyl]amino]-1-oxopentan-2-yl]amino]-5-oxopentanoic acid | 1373119-63-1

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-[4-[[1-(carboxymethyl)triazol-4-yl]methoxy]phenyl]ethyl]amino]-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
• CAS: 1373119-63-1
• 化学式: C₈₃H₁₄₅N₄₃O₁₉S
• 分子量: 2081.41
• InChiKey: AZLZBCOSFPFQQT-KYKFPJIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -9.8
• 重原子数：
  146
• 可旋转键数：
  82
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  1100
• 氢给体数：
  43
• 氢受体数：
  31

反应信息

• 作为产物：
  描述：

  疊氮乙酸 、 biotinyl-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Glu-Arg-Tyr(prop-2-ynyl)(prop-2-ynyl)-OH 在 disodium hydrogenphosphate 、 copper(ll) sulfate pentahydrate 、 盐酸胍 、 三(2-羰基乙基)磷盐酸盐 作用下， 以 水 为溶剂， 反应 1.0h， 以52%的产率得到(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-[4-[[1-(carboxymethyl)triazol-4-yl]methoxy]phenyl]ethyl]amino]-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Tyrosine modified analogues of the α4β7 integrin inhibitor biotin-R8ERY prepared via Click Chemistry: Synthesis and biological evaluation

  摘要：

  Our continuing programme aiming at developing inhibitors of integrin alpha 4 beta 7, a key mediator of various inflammatory diseases, led us to synthesise a library of cell-permeable peptides based on the biotin-R8ERY* template, wherein the tyrosine residue has been modified by using the CuAAC reaction. The peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit Mn2+-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. Two of the synthesised peptidomimetics, analogues 11 and 14, are more active than our previously reported lead compound biotin-r(9)YDRREY at concentrations of 100 and 50 mu M, with 14 exhibiting an IC50 of less than 10 mu M. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.035

文献信息

• Tyrosine modified analogues of the α4β7 integrin inhibitor biotin-R8ERY prepared via Click Chemistry: Synthesis and biological evaluation
  作者：Stefanie Papst、Anaïs Noisier、Margaret A. Brimble、Yi Yang、Geoffrey W. Krissansen

  DOI：10.1016/j.bmc.2012.02.035

  日期：2012.4

  Our continuing programme aiming at developing inhibitors of integrin alpha 4 beta 7, a key mediator of various inflammatory diseases, led us to synthesise a library of cell-permeable peptides based on the biotin-R8ERY* template, wherein the tyrosine residue has been modified by using the CuAAC reaction. The peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit Mn2+-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. Two of the synthesised peptidomimetics, analogues 11 and 14, are more active than our previously reported lead compound biotin-r(9)YDRREY at concentrations of 100 and 50 mu M, with 14 exhibiting an IC50 of less than 10 mu M. (C) 2012 Elsevier Ltd. All rights reserved.