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Compound interaction screen on a photoactivatable cellulose membrane (CISCM) identifies drug targets

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Item Type:Article
Title:Compound interaction screen on a photoactivatable cellulose membrane (CISCM) identifies drug targets
Creators Name:Melder, F.T., Lindemann, P., Welle, A., Trouillet, V., Heißler, S., Nazaré, M. and Selbach, M.
Abstract:Identifying the protein targets of drugs is an important but tedious process. Existing proteomic approaches enable unbiased target identification but lack the throughput needed to screen larger compound libraries. Here, we present a compound interaction screen on a photoactivatable cellulose membrane (CISCM) that enables target identification of several drugs in parallel. To this end, we use diazirine-based undirected photoaffinity labeling (PAL) to immobilize compounds on cellulose membranes. Functionalized membranes are then incubated with protein extract and specific targets are identified via quantitative affinity purification and mass spectrometry. CISCM reliably identifies known targets of natural products in less than three hours of analysis time per compound. In summary, we show that combining undirected photoimmobilization of compounds on cellulose with quantitative interaction proteomics provides an efficient means to identify the targets of natural products.
Keywords:Drug Discovery, Microarrays, Natural Products, Photoaffinity Labeling, Proteomics
Source:ChemMedChem
ISSN:1860-7179
Publisher:Wiley
Volume:17
Number:19
Page Range:e202200346
Date:6 October 2022
Official Publication:https://doi.org/10.1002/cmdc.202200346
PubMed:View item in PubMed

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