Ac-PLGL

• 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: Ac-PLGL
• 英文别名: Ac-Pro-Leu-Gly-Leu-OH；(2S)-2-[[2-[[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-4-methylpentanoic acid
• 化学式: C₂₁H₃₆N₄O₆
• 分子量: 440.54
• InChiKey: ASNNEEQKPHQPEC-ULQDDVLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ac-PLGL 、 盐酸多柔比星 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 Ac-PLGL-Dox
  参考文献：
  名称：

  Discovery of matrix metalloproteases selective and activated peptide–doxorubicin prodrugs as anti-tumor agents

  摘要：

  To selectively target doxorubicin (Dox) to tumor tissue and thereby improve the therapeutic index and/or efficacy of Dox, matrix metalloproteinases (MMP) activated peptide-Dox prodrugs were designed and synthesized by coupling MMP-cleavable peptides to Dox. Preferred conjugates were good substrates for MMPs, poor substrates for neprilysin, an off-target proteinase, and stable in blood ex vivo. When administered to mice with HT1080 xenografts, conjugates, such as 19, preferentially released Dox in tumor relative to heart tissue and prevented tumor growth with less marrow toxicity than Dox. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.084
• 作为产物：
  描述：

  Ac-PLGLRSK 在 matrix metalloprotease-9 作用下， 以 aq. buffer 为溶剂， 反应 72.0h， 以71%的产率得到Ac-PLGL
  参考文献：
  名称：

  基质金属蛋白酶9催化短寡肽的长度依赖性蛋白水解裂解

  摘要：

  基质金属蛋白酶（MMP）作为降解细胞外基质蛋白的酶，对细胞行为起着重要作用。其中，MMP-9通常以在G / L位点占主导的裂解作用催化蛋白质的降解。最近的高通量筛选表明，当MMP-9的底物是寡肽时，S / L是裂解的一个新的主要位点。在这里，我们检查了N末端取代的短寡肽作为MMP-9底物的切割位点。作为此类N取代小肽研究的第一个例子，我们的结果表明，N端的取代基和肽的长度会显着影响寡肽上切割位点的位置，这为设计小肽衍生物作为MMP-9的底物。©2013 Wiley Periodicals，Inc.

  DOI：

  10.1002/bip.22240

文献信息

• Discovery of matrix metalloproteases selective and activated peptide–doxorubicin prodrugs as anti-tumor agents
  作者：Zilun Hu、Xiangjun Jiang、Charles F. Albright、Nilsa Graciani、Eddy Yue、Mingzhu Zhang、Shu-Yun Zhang、Robert Bruckner、Melody Diamond、Randine Dowling、Maria Rafalski、Swamy Yeleswaram、George L. Trainor、Steven P. Seitz、Wei Han

  DOI：10.1016/j.bmcl.2009.12.084

  日期：2010.2

  To selectively target doxorubicin (Dox) to tumor tissue and thereby improve the therapeutic index and/or efficacy of Dox, matrix metalloproteinases (MMP) activated peptide-Dox prodrugs were designed and synthesized by coupling MMP-cleavable peptides to Dox. Preferred conjugates were good substrates for MMPs, poor substrates for neprilysin, an off-target proteinase, and stable in blood ex vivo. When administered to mice with HT1080 xenografts, conjugates, such as 19, preferentially released Dox in tumor relative to heart tissue and prevented tumor growth with less marrow toxicity than Dox. (C) 2009 Elsevier Ltd. All rights reserved.
• Length-dependent proteolytic cleavage of short oligopeptides catalyzed by matrix metalloprotease-9
  作者：Yibing Huang、Junfeng Shi、Dan Yuan、Ning Zhou、Bing Xu

  DOI：10.1002/bip.22240

  日期：2013.11

  Matrix metalloproteinases (MMPs), as the enzymes to degrade extracellular matrix proteins, play a major role on cell behaviors. Among them, MMP‐9 usually catalyzes the degradation of proteins with the dominant cleavage at G/L site. Recent high‐throughput screening suggests that S/L is a new major site for the cleavage when the substrates of MMP‐9 are oligopeptides. Here we examine the cleavage sites

  基质金属蛋白酶（MMP）作为降解细胞外基质蛋白的酶，对细胞行为起着重要作用。其中，MMP-9通常以在G / L位点占主导的裂解作用催化蛋白质的降解。最近的高通量筛选表明，当MMP-9的底物是寡肽时，S / L是裂解的一个新的主要位点。在这里，我们检查了N末端取代的短寡肽作为MMP-9底物的切割位点。作为此类N取代小肽研究的第一个例子，我们的结果表明，N端的取代基和肽的长度会显着影响寡肽上切割位点的位置，这为设计小肽衍生物作为MMP-9的底物。©2013 Wiley Periodicals，Inc.