Poly(ethylene glycol) grafted polystyrene dendrimer resins: Novel class of supports for solid phase peptide synthesis

Poly(propyleneglycol)dimethacrylate cross-linked support using monomers Styrene and 4-chloromethyl styrene (PS-PPGDMA-VBC resin) was prepared by suspension polymerization method. Dendritic templates were synthesized from Schiff base and trimesic acid molecules and assembled independently on PS-PPGDMA-VBC support to the second generation. N,N-bischloro ethyl amine dendrimer was generated from Schiff base units and introduced to the chloromethyl groups uniquely through secondary amine. It was followed by acidolytic cleavage, diazotization and thionyl chloride reactions leading to first generation dendrimer. O-benzyl ether dendrimer was created using 1,3,5-tris(hydroxyl methyl)benzene unit which was produced by the LiAlH₄ reduction of carbonyl groups of trimesic acid molecule. The hydroxyl methyl groups formed were converted to chloro methyl groups by adding thionyl chloride that leads to first generation dendrimer. Similar synthetic routes were followed to produce second generation dendrimers too. Poly(ethylene glycol), M_n ≈ 1500) has been grafted to chlorine termini of both dendrimers and used to check various physical and chemical properties of different peptide synthetic conditions. Reactions were qualitatively analyzed by FTIR, ¹³C NMR, SEM and quantitatively analyzed by UV measurements and CHN analysis. Classically difficult ACP sequence was synthesized on both PEGylated dendrimer supports and compared to Tenta Gel. Biologically significant disulfide bonded endothelin class of peptides were also synthesized using novel supports using various literature reported methods.