Propargyl-PEG4-thiol

Propargyl-PEG4-thiol is a PEG-based bifunctional linker designed for modular assembly of targeted protein degradation constructs. Its combination of a terminal alkyne and a thiol enables orthogonal conjugation strategies that support efficient attachment of ligands while preserving linker flexibility and solubility. This product is particularly useful in PROTAC workflows where robust, reproducible linker chemistry is required; detailed structural and reactivity considerations are provided below.

Structure: Propargyl-PEG4-thiol contains a polyethylene glycol spacer that confers hydrophilicity and conformational flexibility, terminated by a propargyl (alkyne) group and a thiol functionality. The molecule features ether linkages within the PEG chain and carbon–carbon and carbon–sulfur bonds at the termini, supporting stable, handle-rich conjugation chemistry.

Reactivity: The terminal thiol can be used for thioether formation or for thiol–maleimide type coupling under mild conditions, while the terminal alkyne supports copper-catalyzed azide–alkyne cycloaddition or related click conjugations when an azide partner is available. Typical PROTAC linker assembly employs inert atmospheres, compatible organic/aqueous solvent mixtures, and standard base or catalyst systems appropriate to the chosen coupling mode, with careful control of thiol oxidation state to maintain reactivity.