novolactone | 1804950-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: novolactone
• 英文别名: Novolactone；(1R,2S,6R,7S,9R,10S,11S,14S)-5-ethenyl-9,10-dihydroxy-1,6,11-trimethyl-13-oxatetracyclo[8.6.0.02,7.011,14]hexadec-4-en-12-one
• CAS: 1804950-46-6
• 化学式: C₂₀H₂₈O₄
• 分子量: 332.44
• InChiKey: GPFXZYJYVUTNSE-LCPICFLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  novolactone 在 水 作用下， 生成 novolactonic acid
  参考文献：
  名称：

  The Novolactone Natural Product Disrupts the Allosteric Regulation of Hsp70

  摘要：

  The highly conserved 70 kDa heat shock proteins (Hsp70) play an integral role in proteostasis such that dysregulation has been implicated in numerous diseases. Elucidating the precise role of Hsp70 family members in the cellular context, however, has been hampered by the redundancy and intricate regulation of the chaperone network, and relatively few selective and potent tools. We have characterized a natural product, novolactone, that targets cytosolic and ER-localized isoforms of Hsp70 through a highly conserved covalent interaction at the interface between the substrate-binding and ATPase domains. Biochemical and structural analyses indicate that novolactone disrupts interdomain communication by allosterically inducing a conformational change in the Hsp70 protein to block ATP-induced substrate release and inhibit refolding activities. Thus, novolactone is a valuable tool for exploring the requirements of Hsp70 chaperones in diverse cellular contexts.

  DOI：

  10.1016/j.chembiol.2014.11.007

文献信息

• The Novolactone Natural Product Disrupts the Allosteric Regulation of Hsp70
  作者：A. Quamrul Hassan、Christina A. Kirby、Wenlai Zhou、Tim Schuhmann、Roman Kityk、D. Randal Kipp、Jason Baird、Jinyun Chen、Yaoyu Chen、Franklin Chung、Dominic Hoepfner、N. Rao Movva、Raymond Pagliarini、Frank Petersen、Christopher Quinn、Douglas Quinn、Ralph Riedl、Esther K. Schmitt、Anne Schitter、Travis Stams、Christian Studer、Pascal D. Fortin、Matthias P. Mayer、Heather Sadlish

  DOI：10.1016/j.chembiol.2014.11.007

  日期：2015.1

  The highly conserved 70 kDa heat shock proteins (Hsp70) play an integral role in proteostasis such that dysregulation has been implicated in numerous diseases. Elucidating the precise role of Hsp70 family members in the cellular context, however, has been hampered by the redundancy and intricate regulation of the chaperone network, and relatively few selective and potent tools. We have characterized a natural product, novolactone, that targets cytosolic and ER-localized isoforms of Hsp70 through a highly conserved covalent interaction at the interface between the substrate-binding and ATPase domains. Biochemical and structural analyses indicate that novolactone disrupts interdomain communication by allosterically inducing a conformational change in the Hsp70 protein to block ATP-induced substrate release and inhibit refolding activities. Thus, novolactone is a valuable tool for exploring the requirements of Hsp70 chaperones in diverse cellular contexts.