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.
Jiarpinitnun
Chutima
C
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Kiessling
Laura L
LL
D002462:Cell Membrane / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020298:U937 Cells
D008024:Ligands; D010455:Peptides; D044042:Receptors, Formyl Peptide; D011092:Polyethylene Glycols