(2-Pyridyldithio)-PEG4-propargyl
CAS No.: 2170240-99-8
Cat No.: BP-501531
Purity: 98%
4.5 
(2-Pyridyldithio)-PEG4-propargyl is a heterobifunctional PEG-based linker designed for PROTAC and targeted protein degradation workflows that require controlled, thiol-reactive conjugation. Structurally, it contains a terminal propargyl group for copper-catalyzed azide–alkyne cycloaddition (click) coupling and a pyridyldithio moiety that can undergo thiol–disulfide exchange, enabling reversible formation of a disulfide-linked connection to cysteine-containing ligands or engineered protein-binding modules. The PEG4 spacer provides aqueous solubility and conformational flexibility, helping to reduce steric interference and to maintain productive geometry between the two PROTAC components. In PROTAC design, this linker supports modular assembly: the propargyl handle facilitates attachment to an azide-bearing partner, while the pyridyldithio group allows incorporation of thiol-functionalized targeting or E3 ligase ligands via disulfide chemistry. Its value lies in enabling efficient, site-selective conjugation strategies that can improve synthesis reliability and allow systematic exploration of linker effects on degradation potency and selectivity.
Structure of 2170240-99-8
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This PEG-based bifunctional linker, featuring a pyridyl disulfide and a terminal propargyl group, is designed for modular assembly of PROTACs that require controlled attachment to ligands and efficient formation of productive ternary complexes. Its flexible polyethylene glycol scaffold can improve solubility and enable favorable linker conformations, while the disulfide handle supports ligand exchange strategies. The detailed structural and reactivity characteristics are provided below.
Structure: The linker contains a polyethylene glycol chain providing conformational flexibility, a propargyl (alkyne) terminus for click-type conjugation, and a pyridyl disulfide moiety that serves as a thiol-reactive electrophile. It includes ether linkages along PEG and sulfur–sulfur bonds within the disulfide, enabling reversible exchange chemistry.
Reactivity: The pyridyl disulfide reacts with thiols under mild, aqueous-compatible conditions via disulfide exchange, releasing a pyridyl-thiol leaving group and generating a new disulfide linkage to the partner ligand. The propargyl group is suitable for copper-catalyzed azide–alkyne cycloaddition or related alkyne-based coupling approaches, typically using standard click reagents, inert atmosphere when required, and solvents such as aqueous buffer mixtures to maintain solubility and reactivity.
* 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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