Unexpected enhancement in biological activity of a GPCR ligand induced by an oligoethylene glycol substituent.

Polyethylene glycol (PEG) is widely used, and many biologically active molecules are modified with oligoethylene glycol substituents to enhance their half-lives in circulation. The pervasive use of PEG substituents is partly due to their presumed inertness. Our investigation of formyl peptide receptor (FPR)-mediated chemotaxis reveals that oligoethylene glycol substitution can enhance the ability of the peptide chemoattractant N-formyl-methionine-leucine-phenylalanine (fMLF) to activate signal transduction through FPR, a transmembrane G-protein-coupled receptor.