Michael addition of thiol compounds on ω-maleate poly(ethylene oxide)s: Model study for the “site-specific” modification of proteins

In this study, we successfully synthesized ω-maleate poly(ethylene oxide)s (PEOs) as the modifier for proteins through the thiol-ene Michael addition reaction. Both α-azido-ω-maleate PEO and α-t-butoxy-ω-maleate PEO were obtained from the reaction of ‘living’ polymeric alkoxides with maleic anhydride (over 98 mol%). To examine their availability as one of basic matrices for the thiol-ene Michael addition, model compounds as the precursors of protein carrying the thiol group such as thioacetic acid, cysteamine, and cysteine were employed. Their addition on the maleate group was over 98 mol% under sonication or ultraviolet (UV) irradiation. The acidic condition appeared to affect to yield a diastereomeric mixture. All the PEOs carrying the ω-maleate group appeared to be applied for the efficient modifiers in the “site-specific” PEGylation of peptides or proteins. All the functionalized PEOs including ω-succinate PEO were characterized by a combination of size exclusion chromatographic (SEC), 1H nuclear magnetic resonance (NMR), and Fourier transform-infrared (FT-IR) spectroscopic analyses.