Molecular glues and PROTACs: Unlocking targeted protein degradation in plant biology.
Donderis-Fagoaga C, Orea-Ordóñez L, Lozano-Juste J
Crop Improvement
Farmers struggling with herbicide-resistant weeds could one day deploy targeted protein destroyers that shut down only the weed's key survival proteins — without touching the crop beside it.
Every living cell is full of proteins that control how it grows, defends itself, and responds to stress. Scientists have invented molecular tools that act like guided missiles — they latch onto a specific unwanted protein and drag it to the cell's own trash-disposal system to be destroyed. This review explains how those tools work and argues that plant scientists should start using them too, since almost no one has tried yet.
Key Findings
Molecular glues and PROTACs can eliminate proteins previously considered 'undruggable' — including ones with no obvious chemical handle, like transcription factors — by hijacking the cell's own waste-disposal machinery.
Several protein-degrader drug candidates have already reached human clinical trials, validating the approach, yet almost no equivalent tools have been developed for plants or agriculture.
Key design challenges for plant-specific degraders include identifying suitable plant E3 ligase enzymes to co-opt, choosing the right protein targets, and optimizing the chemical linker that connects the two ends of a PROTAC molecule.
chevron_right Technical Summary
Scientists are developing chemical tools called molecular glues and PROTACs that can selectively destroy specific proteins inside cells. This review explores how these human drug-discovery techniques could be adapted for plants, opening new ways to control plant biology and improve crops.
Abstract Preview
Targeted protein degradation (TPD) has emerged as a chemical strategy to modulate proteostasis, offering important advantages over traditional small molecules. By inducing proximity between a prote...
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