Thalidomide-NH-PEG2-C2-NH2 TFA

Background Introduction

Thalidomide-NH-PEG2-C2-NH2 TFA is a specialized E3 ligase ligand-linker conjugate widely used in the field of targeted protein degradation, particularly in PROTAC (Proteolysis Targeting Chimera) technology. It incorporates a thalidomide derivative, which functions as an E3 ubiquitin ligase ligand, and a flexible PEG-based linker, enhancing water solubility and cellular permeability for advanced drug discovery research.

Mechanism

Thalidomide-NH-PEG2-C2-NH2 TFA operates as a critical building block in PROTAC technology by leveraging the thalidomide moiety to recruit the CRBN (cereblon) E3 ubiquitin ligase complex. The PEG2-C2 linker connects the thalidomide to a functional amine group, which allows for further conjugation to ligands targeting specific proteins of interest. Once assembled into a complete PROTAC, the bifunctional molecule draws the target protein and CRBN E3 ligase into close proximity, promoting ubiquitination and subsequent proteasomal degradation of the target protein, thus achieving targeted protein knockdown.

Applications

This E3 ligase ligand-linker conjugate is primarily employed in the synthesis of PROTACs and other protein degradation platforms. Thalidomide-NH-PEG2-C2-NH2 TFA is ideal for medicinal chemistry and chemical biology research focused on creating novel degraders for undruggable targets, validating new drug targets, and studying cellular protein functions. Its versatile amine handle enables conjugation with a wide range of ligands, making it a valuable resource for both academic and pharmaceutical industries engaged in next-generation therapeutics and proteome-wide degradation studies.

• Dual amine functional groups enable versatile conjugation for custom PROTAC design.
• Polyethylene glycol (PEG2) spacer improves solubility and pharmacokinetic properties in CRBN-targeted PROTAC applications.