Solid-Phase Peptide Synthesis of Endothelin Receptor Antagonists on Novel Flexible, Styrene—Acryloyloxyhydroxypropyl Methacrylate—Tripropyleneglycol Diacrylate [SAT] Resin

摘要

Novel cross-linked polymeric support by the copolymerization of styrene and 3-(acryloyloxy)-2-hydroxypropyl methacrylate with Tri(propyleneglycol) diacryalte (SAT) for solid-phase peptide synthesis is presented here. The synthesis of SAT is based on the cross-linking of 3-(acryloyloxy)-2-hydroxypropyl methacrylate with styrene by free-radical suspension polymerization, consisting of an ester and a secondary hydroxyl group. An additional cross-linker tri(propyleneglycol) diacryalte provides a hydrophilic environment throughout the resin, which will enhance the physicochemical properties of the resin toward organic synthesis. The resins were synthesized in various cross-linking densities to check the swelling property, mechanical stability, and functional loading capacity. The resin was characterized by the IR, ~(13)C NMR, and SEM techniques. The extent of swelling properties of the polymer of different cross-linking densities were studied and compared with Merrifield resin and TentaGel. To demonstrate the efficiency of SAT support was proved by synthesizing the challenging peptide sequence of acyl carrier protein (ACP) and compared with commercially available Merrifield resin. It was further tested by synthesizing endothelial receptor antagonist peptides using SAT resin and compared with commercially available TentaGel resin. The standard Fmoc strategy was adopted for peptide synthesis and was characterized by MALDI-TOF MS and analyzed the purity of peptides by HPLC.