Syntheses, characterization and application of crosslinked polystyrene-ethyleneglycol acrylate resin (CLPSER) as a novel polymer support for polypeptide syntheses

Cross-linked polystyrene-ethyleneglycol acrylate resin (CLPSER) was develop ed for the solid-phase synthesis of peptide by introducing a cross-linker O ,O'- bis(2-acrylamidopropyl)polyethylene glycol(1900) (Acr(2)PEG), into pol ystyrene. The cross-linker was prepared by treating acryloyl chloride with O,O'-bis(2-aminopropyl) polyethylene glycol(1900) [(NH2)(2)PEG] in the pres ence of diisopropylethylamine. The copolymer was prepared either by bulk or inverse suspension copolymerization of Acr(2)PEG(1900) and styrene using s orbitan monolaurate as the suspension stabilizer, and a mixture of ammonium peroxodisulfate and benzoyl peroxide as the radical initiators. The resin was characterized using gel-phase C-13 NMR, infrared (KBr) spectroscopic te chniques and the morphological features of the resin were investigated usin g scanning electron microscopy photographs. CLPSER showed excellent swellin g in a broad range of solvents and was found to be chemically inert to vari ous reagents and solvents used in solid-phase peptide synthesis. To demonst rate the usefulness of the new resin in polypeptide synthesis, the support was derivatized with an 'internal reference' amino acid (norleucine) and a handle 4-(4-hydroxymethyl-3-methoxy)butyric acid. The new resin was compare d with commercial supports such as Merrifield and Sheppard resins by synthe sizing an acyl carrier protein (65-74) fragment under the same experimental conditions. HPLC profiles revealed the high efficiency of the newly develo ped support. Resin capability in peptide synthesis was further demonstrated by the solid phase synthesis of a 25-residue peptide from the E2/NS1 regio n hepatitis C viral polyprotein.