Positional Scanning Peptide Libraries for Kinase Substrate Specificity Determinations: Straightforward and Reproducible Synthesis Using Pentafluorophenyl Esters

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• 作者：Thomas Ljungdahl ; Jenny Veide-Vilg ; Fredrik Wallner ; Markus J. Tams ; Morten Grø ; tli
• 刊名：Journal of Combinatorial Chemistry
• 出版年：2010
• 出版时间：September 13, 2010
• 年：2010
• 卷：12
• 期：5
• 页码：733-742
• 全文大小：384K
• 年卷期：v.12,no.5(September 13, 2010)
• ISSN：1520-4774

文摘

An efficient method to synthesize positional scanning synthetic combinatorial libraries (PS-SCLs) for studying the specificity of protein kinases is presented. Isokinetic ratios for pentafluorophenyl esters were determined iteratively using a new approach incorporating high performance liquid chromatography (HPLC) quantification and statistical experimental design. In the development process a large amount of work was put in to find efficient ways of screening for new isokinetic mixtures and to optimize the process of PS-SCL synthesis. The newly developed methods for the screening of isokinetic mixtures could be used for the screening of other interesting mixtures, but more importantly, the isokinetic ratios determined for the preactivated pentafluorophenyl esters were incorporated into a new efficient protocol. This straightforward protocol allows for a convenient synthesis of high quality PS-SCLs regardless of previous experience in solid phase synthesis.