Polyethyleneglycol graft copoly (styrene-1,4-butanediol dimethacrylate) resin for gel-phase peptide synthesis

Summary Synthesis and characterization of a flexible crosslinked polystyrene grafted polyethyleneglycol (PEG) resin which allows for efficient synthesis of aggregating peptides in high yield and purity has been described. The resin showed rigidity, mechanical and chemical stability, and improved swelling and solvation characteristics essential for the successful synthesis of peptides. To demonstrate the usefulness of the new resin in polypeptide synthesis, a 4-(hydroxymethyl)phenoxyacetic acid (HMPA) handle was anchored to the free terminus of PEG and a typical hydrophobic peptide, Alzheimer’s β-amyloid plaque protein (33–42) fragment, was synthesized using Fmoc/tBu tactics. The new resin was compared with commercially available 1 mol% divinylbenzene (DVB)-crosslinked Tentagel resin under identical conditions. HPLC profiles and LC/MS analyses of the crude products revealed the high synthetic efficiency of the newly developed support. Efficiency of the resin was further illustrated by the gel-phase synthesis of a 15-residue peptide, (28–42) fragment of β-amyloid protein.