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000301267 037__ $$aDKFZ-2025-00952
000301267 041__ $$aEnglish
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000301267 1001_ $$00000-0002-1252-1829$$aSchwalm, Martin P$$b0
000301267 245__ $$aBiochemical investigation of LC3/GABARAP-ligand interaction as an important quality measure for LC3/GABARAP-targeting small molecules: addendum to the guidelines (4th edition).
000301267 260__ $$aAbingdon, Oxon$$bTaylor & Francis$$c2025
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000301267 520__ $$aTargeted protein degradation (TPD) represents a new therapeutic modality that allows the targeting of proteins that are considered undruggable by conventional small molecules. While TPD approaches via the ubiquitin-proteasome system are well established and validated, additional degradation pathways still require rigorous characterization. Here, we focus on macroautophagy/autophagy tethering compounds, a class of small molecules, designed to recruit cargo to LC3/GABARAP proteins for subsequent autophagosome-dependent degradation. We provide guidance for the biophysical and structural characterization of small molecule modulators for studying LC3/GABARAP-ligand interactions. In addition, we discuss potential limitations of autophagy-based TPD systems and emphasize the need for rigorous quality control in the development of LC3/GABARAP-targeting small molecules.Abbreviations: DSF: differential scanning fluorimetry; FP: fluorescence polarization; FRET: Förster/fluorescence resonance energy transfer; HTRF: homogeneous time-resolved fluorescence; ITC: isothermal titration calorimetry; LIR: LC3-interacting region; MGs: molecular glues; NMR: nuclear magnetic resonance; PROTACs: PROteolysis-TArgeting Chimeras; SPR: surface plasmon resonance; TPD: targeted protein degradation; TR-FRET: time-resolved Förster/fluorescence resonance energy transfer; UPS: ubiquitin-proteasome system.
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000301267 650_7 $$2Other$$aATTECs
000301267 650_7 $$2Other$$aAUTACs
000301267 650_7 $$2Other$$aAtg8
000301267 650_7 $$2Other$$aGABARAP
000301267 650_7 $$2Other$$aLC3
000301267 7001_ $$aLenz, Christopher$$b1
000301267 7001_ $$0P:(DE-HGF)0$$aSaxena, Krishna$$b2
000301267 7001_ $$00000-0002-7828-8118$$aKlionsky, Daniel J$$b3
000301267 7001_ $$aProschak, Ewgenij$$b4
000301267 7001_ $$00000-0001-5995-6494$$aKnapp, Stefan$$b5
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