Synthesis and evaluation of activity-based probes carrying a 5′-fluorosulfonylbenzoyl adenosine moiety for protein kinases

Abstract

Protein kinases are involved in many important cellular signaling pathways. Development of activity-based probes targeting this enzyme family would be of great contemporary values. In this study, we established a synthetic route that allows parallel synthesis for the preparation of a 2 × 2 probe library. The probes feature a reactive fluorosulfonylbenzoyl moiety on an adenosine framework to investigate the effect of two structural variables on the labeling performance toward kinases. Preliminary labeling results indicated that probe 3, which is the best candidate in the probe library, is indeed an activity-based probe for kinases. The results also revealed that the ester linkage between the fluorosulfonylbenzoyl moiety and the sugar plays an important role in the labeling ability of the probes, and the meta-substituted sulfonyl fluoride could help improving the target specificity. The valuable information obtained in this study could be applied for probe improvement in the future. © 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA.