Synthesis of peptide-N-alkylamides on a new PS-TTEGDA polymer support using photolabile anchoring group

Abstract

Peptide-N-alkylamides were synthesised on a new highly solvating copolymer of 4% tetraethyleneglycol diacrylate-cross-linked polystyrene (PS-TTEGDA) support. The polymer was synthesised by suspension polymerisation using a free radical initiator. The synthesis of C-terminal peptide-N-alkylamide involve prior incorporation of a photolabile linker, 3-nitro-4-bromomethylbenzoic acid to the aminomethylated support. The N-alkylamino group act as an anchoring group for the peptide as well as a latent function for the C-terminal modification of the attached peptide. Irradiation of the peptide-resin with 350 nm light in TFE/DCM resulted in the release of peptide-N-alkylamides. Synthetic utility of the new support was demonstrated by the synthesis of Boc-amino acid-N-alkylamides and C-terminal peptide-N-alkyl amides in 75–80% yields and with high purity.