Synthesis, characterization and application of tetraethylene glycol diacrylate crosslinked polystyrene support for gel phase peptide synthesis

Abstract

Styrene and tetraethylene glycol diacrylate (TTEGDA) were copolymerized by the free radical aqueous suspension polymerization technique, employing toluene as the monomer diluent at 80°C. The resulting beads were functionalized by chloromethylation. The copolymer was characterized by IR and high-resolution solid-state ¹³C-NMR techniques. Scanning electron microscopy was employed to observe shape, size, and morphological features of the crosslinked bead copolymer. The swelling capacities of the copolymer were measured in various solvents. Reactivity of the amino functionalized polymer was compared with divinylbenzene-polystyrene (PS) resin. Stability of the copolymer was tested under various peptide synthetic conditions. High capacity chloromethyl TTEGDA-crosslinked PS was employed as a solid support in the synthesis of the hydrophobic peptide Boc(Ala-Leu-Ala)₄-OMe. The coupling and deprotection steps in the synthetic scheme proceeded in near quantitative yields, supporting the positive role of the flexible and hydrophilic crosslinking agent. The fully protected 12-residue peptide was cleaved from the support by a transesterification procedure in 85% overall yield and characterized by thin-layer chromatography, amino acid analysis, and ¹H-NMR.