Open AccessDevelopment of Rapid and Facile Solid‐Phase Synthesis of PROTACs via a Variety of Binding Styles
Author(s) -
Xu Hanqiao,
Kurohara Takashi,
Takano Reina,
Yokoo Hidetomo,
Shibata Norihito,
Ohoka Nobumichi,
Inoue Takao,
Naito Mikihiko,
Demizu Yosuke
Publication year - 2022
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.202200131
Subject(s) - linker , solid phase synthesis , ligand (biochemistry) , combinatorial chemistry , chemistry , ubiquitin ligase , dna ligase , amide , azide , ubiquitin , organic chemistry , biochemistry , computer science , dna , receptor , peptide , gene , operating system
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.