A novel chemically and mechanically stable glycerol-based crosslinked polystyrene support for polypeptide synthesis: a comparative study with Merrifield resin

Abstract

A novel chemically and mechanically stable polymer support for solid-phase peptide synthesis with excellent swelling performance in various organic solvents is described. The crosslinked polymer in its bead form was prepared by the aqueous suspension polymerization of the styrene and tri(propylene glycol) glycerolate diacrylate. The support is unique because the hydroxyl group is introduced into the polymer support in the polymerization step itself, which makes it highly cost effective. The hydroxyl functionality of the crosslinker in the polymer was used as a growth site for peptide synthesis, thus minimizing the incompatibility arising because of the styrene core as compared to styrene-based polymer supports currently used in polypeptide synthesis. The utility of the resin for solid-phase peptide synthesis was tested by the synthesis of a 19-residue peptide amide of the envelope region of hepatitis C viral polyprotein and was compared with Merrifield resin by the 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluoro phosphate/1-hydroxy benzatriazole method with a Rink amide linker. The molecular character of the polymer and the extent of crosslinking density on the dependence of the reactivity of the attached amino groups were investigated by a reactivity study of the amide bond formation of a model Val-Ala dipeptide. Enhanced swelling, the increased rate of aminoacylation, and the high purity of the peptides synthesized on the novel support highlighted the influence of the polarity of the solid support in the solid-phase synthesis.