Azido-PEG4-Val-Cit-PAB-OH
CAS No.: 2055024-64-9
Cat No.: BP-500612
Purity: >98.0%
4.5 
Azido-PEG4-Val-Cit-PAB-OH is a bifunctional PROTAC linker building block featuring a short polyethylene glycol spacer that terminates in an azide handle for orthogonal conjugation, and a protease-cleavable Val–Cit–PAB motif embedded within the linker. Structurally, the PEG4 segment provides conformational flexibility and improves effective proximity between the recruiting ligand and the target-binding ligand while maintaining a defined cleavage-sensitive junction. Functionally, the Val–Cit–PAB arrangement is designed to be recognized by lysosomal proteases after cellular uptake, enabling cleavage to release the active amide-containing fragment and thereby promote productive ubiquitination and targeted protein degradation. In targeted degradation research, this linker supports modular assembly of PROTACs via azide-based coupling strategies, facilitating rapid structure–activity optimization and systematic evaluation of linker length and cleavage efficiency. It is particularly useful when researchers require tunable spatial separation together with a well-established, cleavage-triggered activation strategy.
Structure of 2055024-64-9
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This PROTAC linker reagent, Azido-PEG4-Val-Cit-PAB-OH, is designed to connect a targeting ligand to a cereblon-recruiting moiety through a PEG-based spacer and a protease-sensitive degradation motif. Its azide handle supports efficient bioorthogonal conjugation, while the Val-Cit-PAB sequence is widely used to enable controlled intracellular processing and targeted protein degradation. The following points describe the structure and practical reactivity considerations in detail.
Structure: The linker comprises a polyethylene glycol spacer coupled to a Valine–Citrulline–p-aminobenzyl (PAB) degradation motif and terminates in an azide functional group. It contains stable amide and carbamate-related linkages, an aromatic PAB segment, and ether linkages within the PEG chain, contributing to aqueous compatibility and conformational flexibility.
Reactivity: The terminal azide enables conjugation via azide–alkyne cycloaddition, typically using copper(I) catalysts with appropriate ligands, or using copper-free strain-promoted variants to minimize metal exposure. For PROTAC assembly, the linker is commonly reacted under mild conditions in polar organic/aqueous solvent mixtures compatible with peptide-like motifs. The degradation module is designed to undergo intracellular proteolytic cleavage after ternary complex formation, following established PROTAC mechanism principles.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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