macrocycle (Cbz)Lys-(Boc)Lys-Val-NMe-D-Phe-Phe | 1321842-03-8

• 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: macrocycle (Cbz)Lys-(Boc)Lys-Val-NMe-D-Phe-Phe
• 英文别名: cyclo-(Phe-N-Me-D-Phe-Val-Lys(Boc)-Lys(Cbz))；Phe-N-Me-D-Phe-Val-Lys(Boc)-Lys(Cbz)
• CAS: 1321842-03-8
• 化学式: C₄₉H₆₇N₇O₉
• 分子量: 898.112
• InChiKey: NWVMTUVGBPGRQI-IURJAOHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  65.0
• 可旋转键数：
  17.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  213.37
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  macrocycle (Cbz)Lys-(Boc)Lys-Val-NMe-D-Phe-Phe 在 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 0.75h， 生成 4-[4-[(2S,5S,8R,11S,14S)-8,11-dibenzyl-7-methyl-3,6,9,12,15-pentaoxo-14-[4-(phenylmethoxycarbonylamino)butyl]-5-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]butylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid
  参考文献：
  名称：

  A small molecule that preferentially binds the closed conformation of Hsp90

  摘要：

  Described is the synthesis of three different fluorescein-tagged derivatives of a macrocycle, and their binding affinity to heat shock protein 90 (Hsp90). Using fluorescence polarization anisotropy, we report the binding affinity of these fluorescein-labeled compounds to Hsp90 in its open state and ATP-dependent closed state. We show that the compounds demonstrate a conformation-dependent preference for binding to the closed state. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.09.096
• 作为产物：
  描述：

  Fmoc-L-缬氨酸 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 macrocycle (Cbz)Lys-(Boc)Lys-Val-NMe-D-Phe-Phe
  参考文献：
  名称：

  Synthesis and evaluation of biotinylated sansalvamide A analogs and their modulation of Hsp90

  摘要：

  Described are the syntheses of three sansalvamide A derivatives that contain biotinylated tags at individual positions around the macrocycle. The tagged derivatives indicated in protein pull-down assays that they bind to Hsp90 at the same binding site (N-Middle domain) as the San A-amide peptide. Further, these compounds inhibit binding between Hsp90 and multiple C-terminal client proteins. This interaction is unique to the San A analogs indicating they can be tuned for selectivity against Hsp90 client/ co-chaperone proteins. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.083

文献信息

• Dimerization of a heat shock protein 90 inhibitor enhances inhibitory activity
  作者：Hendra Wahyudi、Yao Wang、Shelli R. McAlpine

  DOI：10.1039/c3ob41722k

  日期：——

  Heat shock protein 90 (hsp90) accounts for 1–2% of the total proteins in normal cells and it functions as a dimer. Hsp90 behaves as a molecular chaperone that folds, assembles, and stabilizes client proteins. We have developed a novel hsp90 inhibitor, and herein we describe the synthesis and biological activity of the dimerized variant of this inhibitor. Tethering a monomer inhibitor together produced a dimerized compound that more effectively inhibits hsp90 over the monomer.

  热休克蛋白 90（hsp90）占正常细胞蛋白质总量的 1-2%，它以二聚体的形式发挥作用。Hsp90 是一种分子伴侣，能折叠、组装和稳定客户蛋白。我们开发出了一种新型 hsp90 抑制剂，在此我们将介绍这种抑制剂二聚体变体的合成和生物活性。将单体抑制剂拴在一起产生的二聚化合物比单体抑制剂更有效地抑制 hsp90。