Azido-PEG3-Val-Cit-PAB-PNP
CAS No.: 2055047-18-0
Cat No.: BP-501460
Purity: >98.0%
4.5 
Azido-PEG3-Val-Cit-PAB-PNP is a bifunctional PROTAC linker designed to connect a targeting ligand to an effector moiety via a modular PEG3 spacer and a protease-cleavable Val–Cit motif. Structurally, it incorporates an azide handle for bioorthogonal conjugation, a short polyethylene glycol segment that improves solubility and reduces steric hindrance, and a self-immolative p- nitrophenyl (PNP) carbonate/ester trigger that can facilitate controlled release of the downstream fragment after activation. In PROTAC architectures, the Val–Cit sequence is commonly used to enable lysosomal protease processing, generating a reactive intermediate that promotes dissociation and subsequent engagement of the recruited protein degradation machinery. This linker is valuable for researchers building degraders that require efficient, site-selective attachment of ligands and predictable intracellular cleavage behavior, supporting systematic optimization of linker length, polarity, and activation kinetics in targeted protein degradation studies.
Structure of 2055047-18-0
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Azido-PEG3-Val-Cit-PAB-PNP, integrates a PEG-based spacer with a protease-cleavable Val-Cit motif and a self-immolative PAB unit terminating in a PNP leaving group. Its modular architecture supports efficient conjugation to targeting ligands and promotes controlled release of the active warhead during targeted protein degradation workflows. The detailed structural and reactivity considerations are provided below.
Structure: The molecule contains an azide handle for bioorthogonal coupling, a flexible polyether (PEG) spacer, and peptide-derived Val-Cit connectivity. A para-aminobenzyl (PAB) self-immolative segment links to a p-nitrophenyl (PNP) ester/triggering group, enabling cleavage-driven cascade behavior.
Reactivity: The azide enables strain-promoted or copper-catalyzed azide–alkyne cycloaddition for assembling PROTAC architectures under standard click chemistry conditions. The Val-Cit/PAB arrangement is designed for protease-mediated cleavage followed by self-immolative fragmentation, which releases the PNP leaving group. Linker incorporation typically uses inert atmospheres, compatible polar aprotic solvents, and routine coupling/click-compatible reagents, with reaction monitoring by chromatographic or spectrometric methods.
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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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