m-PEG5-COOH

m-PEG5-COOH is a polyethylene glycol-based linker designed for assembling PROTACs, offering a hydrophilic, conformationally flexible spacer that can improve solubility and reduce non-specific interactions. Its carboxylic acid functionality enables reliable conjugation to targeting ligands or handles for subsequent coupling steps. The molecule’s PEG character supports favorable linker–protein interface behavior in targeted protein degradation workflows. Detailed structural and reactivity considerations are provided below.

Structure: The linker comprises a PEG oligomer segment terminated by a carboxylic acid, providing ether-rich connectivity and a flexible, solvated chain. It contains ester-like functionality in the acid form, with polar C–O and O–H interactions that enhance water compatibility. The overall scaffold supports conformational adaptability.

Reactivity: The terminal carboxylic acid can be activated for amide bond formation with amine-bearing ligands under standard peptide-coupling strategies. Typical approaches use carbodiimide/auxiliary coupling reagents and a base in polar aprotic solvents, followed by purification to remove coupling byproducts. Mechanistically, activation forms an acyl intermediate that reacts with nucleophilic amines to yield stable amide linkages suitable for PROTAC construction.