biostudies-literatureXu HNaito FoundationSumitomo FoundationNOVARTIS Foundation (Japan) for the Promotion of ScienceTakeda Science FoundationJapan Agency for Medical Research and Developmente202200131https://www.ebi.ac.uk/biostudies/studies/S-EPMC9278092biostudies-literatureUnknown11(7)Optimizing linker design is important for ensuring efficient degradation activity of proteolysis-targeting chimeras (PROTACs). Therefore, developing a straightforward synthetic approach that combines the protein-of-interest ligand (POI ligand) and the ligand for E3 ubiquitin ligase (E3 ligand) in various binding styles through a linker is essential for rapid PROTAC syntheses. Herein, a solid-phase approach for convenient PROTAC synthesis is presented. We designed azide intermediates with different linker lengths to which the E3 ligand, pomalidomide, is attached and performed facile PROTACs synthesis by forming triazole, amide, and urea bonds from the intermediates.ChemistryOpenDevelopment of Rapid and Facile Solid-Phase Synthesis of PROTACs via a Variety of Binding Styles.PMC927809222fk0210110j040122fk0310504j22fk0310506j070122mk0101197j0002Inoue TYokoo HNaito MTakano RDemizu YOhoka NKurohara TXu HShibata NfalseDevelopment of Rapid and Facile Solid-Phase Synthesis of PROTACs via a Variety of Binding Styles.Optimizing linker design is important for ensuring efficient degradation activity of proteolysis-targeting chimeras (PROTACs). Therefore, developing a straightforward synthetic approach that combines the protein-of-interest ligand (POI ligand) and the ligand for E3 ubiquitin ligase (E3 ligand) in various binding styles through a linker is essential for rapid PROTAC syntheses. Herein, a solid-phase approach for convenient PROTAC synthesis is presented. We designed azide intermediates with different linker lengths to which the E3 ligand, pomalidomide, is attached and performed facile PROTACs synthesis by forming triazole, amide, and urea bonds from the intermediates.2022-01-01T00:00:00Z2022 Jul2025-04-19T17:48:14.748Z2022-07-19T09:47:18.462ZS-EPMC92780923582291310.1002/open.202200131