design, synthesis, and characterization of a highly effective hog1 inhibitor a powerful tool for analyzing map kinase signaling in yeast设计、合成和表征的高效hog1抑制剂在酵母map激酶信号分析的有力工具.pdfVIP

Design, Synthesis, and Characterization of a Highly Effective Hog1 Inhibitor: A Powerful Tool for Analyzing MAP Kinase Signaling in Yeast ´ 1. 2. ´ 2. 3 1 Peter Diner , Jenny Veide Vilg , Jimmy Kjellen , Iwona Migdal , Terese Andersson , Marinella 4 4 5 2 3 ´ 2 Gebbia , Guri Giaever , Corey Nislow , Stefan Hohmann , Robert Wysocki , Markus J. Tamas , Morten Grøtli1* ¨ 1 Medicinal Chemistry, Department of Chemistry, University of Gothenburg, Goteborg, Sweden, 2 Microbiology, Department of Cell and Molecular Biology, University of ¨ Gothenburg, Goteborg, Sweden, 3 Institute of Plant Biology, Department of Genetics and Cell Physiology, University of Wroclaw, Wroclaw, Poland, 4 Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada, 5 Department of Molecular Genetics, University of Toronto, Toronto, Canada Abstract The Saccharomyces cerevisiae High-Osmolarity Glycerol (HOG) pathway is a conserved mitogen-activated protein kinase (MAPK) signal transduction system that often serves as a model to analyze systems level properties of MAPK signaling. Hog1, the MAPK of the HOG-pathway, can be activated by various environmental cues and it controls transcription, translation, transport, and cell cycle adaptations in response to stress conditions. A powerful means to study signaling in living cells is to use kinase inhibitors; however, no inhibitor targeting wild-type Hog1 exists to date. Herein, we describe the