DBCO-PEG4-NHS ester

This DBCO-PEG4-NHS ester is a bifunctional linker designed for efficient conjugation in PROTAC-related workflows, enabling rapid attachment of an NHS-activated handle to amine-containing ligands while preserving a bioorthogonal DBCO functionality for subsequent click coupling. Its PEG-based spacer improves solubility and reduces steric interference, supporting reliable assembly of heterobifunctional degraders. The detailed structural and reactivity characteristics are provided below.

Structure: The molecule comprises a DBCO moiety linked through a polyethylene glycol spacer to an N-hydroxysuccinimide ester. It contains an activated carboxylate for amide formation and a cyclooctyne-based strained alkyne for copper-free click chemistry. The PEG segment confers flexibility and improved aqueous compatibility.

Reactivity: The NHS ester reacts with primary amines to form stable amide bonds under mildly basic aqueous or mixed solvent conditions, typically requiring careful control of pH and avoidance of competing nucleophiles. The DBCO group undergoes strain-promoted azide–alkyne cycloaddition with azide-bearing partners without metal catalysts. For PROTAC assembly, sequential conjugation—amine coupling followed by bioorthogonal click—can be performed using compatible buffers and standard purification to remove excess reagents.