Synthesis and characterization of glycerol dimethacrylate cross-linked polymethyl methacrylate: a resin for solid phase peptide synthesis

Abstract

The new glycerol dimethacrylate cross-linked polymethyl methacrylate polymer support (GDMA-PMMA) for solid phase synthesis is presented. The synthesis of GDMA-PMMA resin is based on the cross-linking of GDMA with methyl methacrylate by free radical polymerization, affording a polymer containing ester and secondary hydroxyl groups. The polymer was prepared using benzoyl peroxide as initiator either via bulk polymerization or via suspension polymerization in polyvinyl alcohol, the latter yielding a beaded resin. The polymerization reaction was investigated with respect to the effect of amount of cross-linking agent in order to vary the swelling, loading and the mechanical stability of the resin. The polymer was characterized by FT-IR and ¹³C CP MAS NMR spectroscopic techniques. The solvent uptake of the polymer was studied in relation to cross-linking and compared with Merrifield resin. The stability of the resin was tested in various synthetic conditions used in solid phase peptide synthesis. The resin was derivatized with chloro and amino functional groups. The C-terminal amino acid incorporation, Nα-Fmoc deprotection, acylation reactions and removal of target peptide from the support were optimized. The efficiency of the resin was demonstrated by synthesizing leucyl-alanyl-glycil-valine, alanine-alanine-alanine-alanine, acyl carrier protein (65–74) and retro-acyl carrier protein (74–65) fragments under optimal conditions and is compared with Merrifield resin. The purity of the peptides was checked by HPLC and identities were established by amino acid analysis and mass spectroscopic techniques.