GEL-PHASE PEPTIDE-SYNTHESIS ON A NEW HIGH-CAPACITY TETRAETHYLENEGLYCOL DIACRYLATE-CROSS-LINKED POLYSTYRENE SUPPORT - SYNTHESIS OF PARDAXIN-16-33

An insoluble but highly solvating copolymer composed of tetraethylencg lycol diacrylate (TTEGDA)-crosslinked polystyrene has been prepared in beaded form by free-radical suspension polymerization of the monomers and employed as a new solid support for gel-phase peptide synthesis. This new polymer support has comparable physical and mechanical proper ties as that of the divinylbenzene (DVB)-crosslinked polystyrene suppo rt permitting identical manipulation such as shaking and filtration wh en used as a support for solid-phase peptide synthesis. This polystyre ne-TTEGDA crosslinked polystyrene resin undergoes much more effective swelling and solvation than DVB-crosslinked polystyrene resin undergoe s much more effective swelling and solvation than DVB-crosslinked poly styrene in a range of solvents with widely varying polarity which are commonly employed in peptide synthesis. The resin can be easily chloro methylated under controlled conditions to prepare resins of varying ca pacity ranging from low (0.15 meg/g) to high capacity (3.5 meq/g). A h igh capacity resin with 1.5 meq/g chlorine capacity was used for synth esis of hydrophilic C-terminal 18-residue peptide of pardaxin from Par dachirus Pavoninus. The peptide was cleaved from the polymeric support by trifluoroacetic acid at 37 degrees C and purified by Fast Protein Liquid Chromatography (FPLC). The purified peptide was shown to be hom ogeneous by HPLC and the identity of the 18-residue peptide was confir med by amino acid analysis. The free peptide possesses a disordered co nformation as revealed by the CD measurement.