具有抗癌活性的苔藓抑素简化类似物对PKCdelta-GFP的转位表现出更强的效力。

Simplified analogs of bryostatin with anticancer activity display greater potency for translocation of PKCdelta-GFP.

作者信息

Baryza Jeremy L, Brenner Stacey E, Craske Madeleine L, Meyer Tobias, Wender Paul A

机构信息

Department of Chemistry, Stanford University, Stanford, CA 94305, USA.

出版信息

Chem Biol. 2004 Sep;11(9):1261-7. doi: 10.1016/j.chembiol.2004.06.014.

DOI:10.1016/j.chembiol.2004.06.014

PMID:15380186

Abstract

Structurally simplified analogs of bryostatin 1, a marine natural product in clinical trials for the treatment of cancer, have been shown to be up to 50 times more potent than bryostatin 1 at inducing the translocation of PKCdelta-GFP from the cytosol of rat basophilic leukemia (RBL) cells. The end distribution of the protein is similar for all three compounds, despite a significant difference in translocation kinetics. The potency of the compounds for inducing the translocation response appears to be only qualitatively related to their binding affinity for PKC, highlighting the importance of using binding affinity in conjunction with real-time measurements of protein localization for the pharmacological profiling of biologically active agents.

摘要

苔藓抑素1是一种正在进行癌症治疗临床试验的海洋天然产物，其结构简化的类似物在诱导蛋白激酶Cδ-绿色荧光蛋白（PKCδ-GFP）从大鼠嗜碱性白血病（RBL）细胞胞质溶胶易位方面，已被证明比苔藓抑素1的效力高50倍。尽管易位动力学存在显著差异，但这三种化合物的蛋白质最终分布是相似的。这些化合物诱导易位反应的效力似乎仅在质量上与它们对PKC的结合亲和力相关，这突出了结合结合亲和力与蛋白质定位的实时测量来对生物活性剂进行药理分析的重要性。