% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Schwalm:301267, author = {M. P. Schwalm$^*$ and C. Lenz and K. Saxena$^*$ and D. J. Klionsky and E. Proschak and S. Knapp$^*$}, title = {{B}iochemical investigation of {LC}3/{GABARAP}-ligand interaction as an important quality measure for {LC}3/{GABARAP}-targeting small molecules: addendum to the guidelines (4th edition).}, journal = {Autophagy}, volume = {21}, number = {9}, issn = {1554-8627}, address = {Abingdon, Oxon}, publisher = {Taylor $\&$ Francis}, reportid = {DKFZ-2025-00952}, pages = {2069-2073}, year = {2025}, note = {ISSN 1554-8635 / 2025 Sep;21(9):2069-2073}, abstract = {Targeted 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.}, keywords = {ATTECs (Other) / AUTACs (Other) / Atg8 (Other) / GABARAP (Other) / LC3 (Other)}, cin = {FM01}, ddc = {570}, cid = {I:(DE-He78)FM01-20160331}, pnm = {899 - ohne Topic (POF4-899)}, pid = {G:(DE-HGF)POF4-899}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:40344429}, doi = {10.1080/15548627.2025.2498506}, url = {https://inrepo02.dkfz.de/record/301267}, }