A target-based approach has the advantages that mode of action is, in principle, known right from the outset, enzyme assays are typically reliable and easy to perform, and compound design is often aided by structural biology. Drug discovery typically takes one of two approaches: a target-based approach, where a compound is developed to target a particular enzyme, and phenotypic screening, where libraries of small molecules are screened against live cells with a phenotypic read-out. His research focus is chemical biology and chemical proteomics with emphasis on the reactivity of natural products and their dedicated targets in prokaryotic and eukaryotic cells.ġ Introduction Natural products (NPs) have always been the inspiration for the development of drugs and a source of tools to elucidate cellular mechanisms.
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In 2006 he started his independent research career at the University of Munich (LMU), Germany and in 2009 was appointed full professor at Technische Universität Munich.
Benjamin Cravatt for his postdoctoral work.
Marahiel, University of Marburg and Prof. He did his graduate studies in the labs of Prof. Sieber studied chemistry at the University of Marburg, Germany. Her research interests include chemical tools for studying post-translational modifications, and the development of photoaffinity and activity-based probes to understand host–pathogen interactions and cancer. Stephan Sieber in the Technische Universität Munich. She is currently a Marie Curie Fellow hosted in the lab of Prof. Wright received her MSc in Natural Sciences (Chemistry) from the University of Cambridge in 2008, and then studied for an MRes and PhD (received 2013) in Chemical Biology at Imperial College London with Prof. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. We also discuss ‘competitive mode’ approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. We also focus here on strategies that employ a click reaction, the copper-catalysed azide–alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied “ in situ” – in living systems rather than cell lysates. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today.
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