Solubilization of Hydrophobic Peptides by Reversible Cysteine PEGylation

Conjugation of Polyethylene Glycol via a Disulfide Bond Confers Water Solubility upon a Peptide Model of a Protein Transmembrane Segment

“…Reaction of PEG-a-Cys reagent with ALC peptide in aqueous solution caused no visible color generation, in contrast to the reaction in sodium phosphate buffer (pH 7) reported previously (10). Aqueous reactions were run at pH 5.…”

“…ALC was designed as a synthetic peptide model of a generic TM segment fusion protein (10). The sequence of the ALC peptide, H 2 N-REAAALAAAAALAAWAAL-CPARRRR-CO 2 H, was based on a series of model TM peptides developed in our laboratory which were demonstrated to insert into lipid micelles and form ␣-helical structures (23).…”

“…We initially reported complete PEGylation at a 5:1 molar ratio of PEG-a-Cys reagent to ALC peptide (10). We have now optimized the reaction conditions such that a 1:1 molar ratio is sufficient for complete PEGylation (Fig.…”

“…2), a synthetic peptide model of a generic TM segment fusion protein, to test the effect of PEGylation upon the solubility of a hydrophobic TM segment peptide. A preliminary report of the synthesis of PEG-a-Cys reagent and the reactivity of the unpurified reagent with ALC peptide has appeared (10).…”

Synthesis, Characterization and In Vivo Activity of Salmon Calcitonin Coconjugated With Lipid and Polyethylene Glycol

“…While the phenomenon is not unique in lipidized peptides, for example, insulin conjugated with myristoyl or deoxycholic acid has also been observed to aggregate in aqueous media, 18,19 PEG conjugation has been known to improve peptide solubility and to eliminate peptide aggregation in aqueous media. [20][21][22] Conjugation of Mal-sCT with PEG, even at up to 2PEG chains, however, did not eliminate the aggregation behavior of the lipidized peptide.…”