No Taste for Methyl: Methylation Sensitive Proteolysis in Drug Screening

Bissinger, Elisabeth-Maria; Jung, Manfred

doi:10.1016/j.chembiol.2010.07.001

Cited by 2 publications

(1 citation statement)

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“…Despite the adequacy of this method, the separation was performed on a specialized instrument, which may limit the assay’s potential for drug screening and prevent its broader adoption [117]. To simplify this method, we envision that FP can be used as the detection technique instead of electrophoresis to reveal the different-charge peptides generated by the Endo-LysC treatment by following the principle described in section 2.2.1: under optimal ionic strength conditions, the labeled peptides carrying different net charges can be expected to bind to an opposite-charged poly-amino acid (polylysine/polyarginine or polyglutamic acid) to a different extent, thereby providing an FP window to quantitate the extent of histone peptide methylation (Figure 5).…”

Section: Expert Opinionmentioning

confidence: 99%

Fluorescence polarization assays in small molecule screening

Lea

Simeonov²

2010

Expert Opinion on Drug Discovery

306

225

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Importance of the field Fluorescence polarization (FP) is a homogeneous method that allows rapid and quantitative analysis of diverse molecular interactions and enzyme activities. This technique has been widely utilized in clinical and biomedical settings, including the diagnosis of certain diseases and monitoring therapeutic drug levels in body fluids. Recent developments in the field has been symbolized by the facile adoption of FP in high-throughput screening (HTS) and small molecule drug discovery of an increasing range of target classes. Areas covered in this review The article provides a brief overview on the theoretical foundation of FP, followed by updates on recent advancements in its application for various drug target classes, including G-protein coupled receptors (GPCRs), enzymes and protein-protein interactions (PPIs). The strengths and weaknesses of this method, practical considerations in assay design, novel applications, and future directions are also discussed. What the reader will gain The reader will be informed of the most recent advancements and future directions of FP application to small molecule screening. Take home message In addition to its continued utilization in high-throughput screening, FP has expanded into new disease and target areas and has been marked by increased use of labeled small molecule ligands for receptor binding studies.

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Section: Expert Opinionmentioning

confidence: 99%