macrocycle Val-NMe-D-Phe-Lys-(Cbz)Lys-Leu | 1321841-86-4

• 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 Val-NMe-D-Phe-Lys-(Cbz)Lys-Leu
• 英文别名: Lys-N-Me-D-Phe-Val-Leu-Lys(Cbz)
• CAS: 1321841-86-4
• 化学式: C₄₁H₆₁N₇O₇
• 分子量: 763.978
• InChiKey: ZOGZDIUUVHDCOR-ISWDJSIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  55.0
• 可旋转键数：
  16.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  201.06
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  macrocycle Val-NMe-D-Phe-Lys-(Cbz)Lys-Leu 、 6-carboxyfluorescein N-hydroxysuccinimide ester 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以8 mg的产率得到4-[4-[(2S,5S,8S,11S,14R)-14-benzyl-13-methyl-8-(2-methylpropyl)-3,6,9,12,15-pentaoxo-5-[4-(phenylmethoxycarbonylamino)butyl]-11-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：

  N-芴甲氧羰酰基-N-甲基-D-苯丙氨酸 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 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-) 、 三氟乙酸 、 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 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 0.75h， 生成 macrocycle Val-NMe-D-Phe-Lys-(Cbz)Lys-Leu
  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

文献信息

• Synthesis and evaluation of biotinylated sansalvamide A analogs and their modulation of Hsp90
  作者：Joseph B. Kunicki、Mark N. Petersen、Leslie D. Alexander、Veronica C. Ardi、Jeanette R. McConnell、Shelli R. McAlpine

  DOI：10.1016/j.bmcl.2011.06.083

  日期：2011.8

  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.