Conjugation of polyethylene glycol via a disulfide bond confers water solubility upon a peptide model of a protein transmembrane segment.

The aqueous insolubility of hydrophobic peptides has presented a barrier to the structural characterization of membrane protein transmembrane domains. Since the conjugation of polyethylene glycol is known to modulate the solubility of certain proteins and peptides, we have prepared PEG-a-Cys reagent, a polyethylene glycol derivative which reacts spontaneously with Cys residues to attach polyethylene glycol to polypeptides via a mixed disulfide bond. When desired, the PEG moiety can be readily removed by reduction with tricarboxyethylphosphine. The aqueous solubilizing power of PEG-a-Cys reagent is confirmed with a synthetic hydrophobic peptide model of a generic transmembrane segment-soluble carrier fusion protein. Copyright 1999 Academic Press.