3,4-Dibromo-Mal-PEG4-Boc

This PROTAC linker, 3,4-Dibromo-Mal-PEG4-Boc, is designed to provide a PEG-based spacer combined with orthogonally addressable functional handles for assembling targeted protein degradation constructs. Its flexible ethylene glycol segment can help tune linker solubility and spatial presentation between targeting and recruiting modules, while the tert-butyl ester-protected carboxyl functionality supports controlled synthetic sequencing. The subsequent sections describe its structural features and practical reactivity considerations for PROTAC synthesis.

Structure: The linker contains a PEG4 polyether chain that imparts conformational flexibility and improved aqueous compatibility. It also features a 3,4-dibromomaleimide core and a tert-butyl ester-protected carboxyl group, providing chemically distinct sites for subsequent functionalization. The scaffold includes ester and imide linkages.

Reactivity: The 3,4-dibromomaleimide motif is thiol-reactive and can undergo thiol addition/substitution at the brominated maleimide alkene under appropriate conditions. The tert-butyl ester is typically preserved under mild base conditions and removed under acidolysis to reveal a carboxylic acid when required for coupling. For PROTAC assembly, reactions are generally performed in polar aprotic or mixed solvent systems using conditions compatible with PEG linkers and thiol-sensitive maleimide chemistry.