高等学校化学学报2011，Vol.32Issue(1)：88-94,7.
Rugulosin对N-Hsp90的抑制与结合作用
Inhibitation and Binding of Rugulosin with N-Hsp90
摘要
Abstract
Rugulosin firstly isolated from the metabolites of Penicillium rugulosum Thom has a strong inhibitory activity on Streptococcus and Corynebacterium. Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of a number of signalling proteins and protein kinases that promote cancer cell growth or survival. By molecular docking, we found the combination between Rugulosin and N-Hsp90 (N-terminal of Hsp90, the ATPase activity domain). Rugulosin showed strong inhibition to ATPase activity of Hsp90 and the IC5o was 22.3μmol/L in vitro experiments. In this study, the interaction mechanism of Rugulosin with N-Hsp90 was investigated by fluorescence, ForteBio Octet, circular dichroism, UV-Visible absorption spectroscopy, SPR technology and Western Blot. Fluorescence spectra experiment results showed that Rugulosin caused a strong fluorescence quenching on intrinsic fluorescence of Hsp90 by static quenching method. Thermodynamic analysis signified the binding mechanism was hydrogen forces and dissociation constant was 22. 4μmol/L, which was 85.9 μmol/L calculated from ForteBio Octet method. Circular dichroism spectra detected the α-helix of N-Hsp90 reduced as the concentration of Rugulosin increased. Rugulosin could also down-regulate the expression of the client protein Akt and Raf-l in HeLa cells. This study illustrates that Ruglulosin, which inhibited the ATPase activity of Hsp90 through interacting with N-Hsp90, may be a potential inhibitor of Hsp90.关键词
Rugulosin/Hsp90/荧光光谱/圆二色光谱/表面等离子体共振Key words
Rugulosin/ Hsp90/ Fluorescence spectroscopy/ Circular dichroism spectroscopy/ Surface plasmon resonance分类
化学化工引用本文复制引用
陈俊杰,易玉婷,于淼,薛少龙,熊茜茜,贺晓萌,张连茹..Rugulosin对N-Hsp90的抑制与结合作用[J].高等学校化学学报,2011,32(1):88-94,7.基金项目
国家自然科学基金(批准号:30873148,30973566,30921005,90913024)和国家"重大新药创制"科技重大专项(批准号:2009ZX09103-083)资助. （批准号:30873148,30973566,30921005,90913024）
