Chemical biology toolkit for exploring protein kinase catalyzed phosphorylation reactions

Abstract

EDGE ARTICLEAndrew J. deMello, Joshua B. Edel et al. Rapid cell extraction in aqueous twophase microdroplet systems PERSPECTIVE Barry M. Trost et al. Catalytic asymmetric allylic alkylation employing heteroatom nucleophiles: a powerful method for C-X bond formation Abstract Current interests in biochemical transformations based on protein kinase-catalyzed phosphorylations drive the identification and characterization of biological targets and potential inhibitors of protein kinase activity. A simple transfer of a phosphate group from adenosine triphosphate (ATP) to the Ser/Thr/Tyr residues of target proteins drives cellular processes, including cell expression, growth, and death. Currently, three major experimental approaches towards kinome analysis are available a) genetic engineering of protein kinases, b) modifications of target substrates, and c) derivatization of ATP co-substrate. Each approach offers advantages but also has disadvantages, which are discussed in this perspective, alongside with a rationale for designing and developing biological tools for kinome study.

A Bioorganometallic Approach to Study Histidine Kinase Autophosphorylations

“…These works demonstrated that Fc‐ATP and its derivative compounds are powerful tools for protein‐kinase‐activity and inhibitor‐screening studies. Even though γ‐modified ATP was demonstrated to be acceptable as a substrate in HK‐mediated processes, Fc‐labelled ATP was still unknown . Thus, we decided to examine the usefulness of this tool in this biological process (Scheme ).…”

Alternative synthetic tools to phospho-specific antibodies for phosphoproteome analysis: progress and prospects

“…The methods used in this burgeoning field have been recently and comprehensively reviewed from kinase identification [3], analytical chemistry [4], and chemical biology toolkit [5] perspectives and the main approaches are briefly overviewed below.…”

Long‐Wavelength Fluorescent Reporters for Monitoring Protein Kinase Activity

“…Although a variety of fluorescent sensors of protein kinases have been described, [7]–[8] strategies have not yet been developed that can tune sensors to specific wavelengths within the optical window of tissue. One appealing approach is to take advantage of the commercial availability of far-red and near-IR fluorophores.…”