The design and synthesis of peptide/protein based ATRP initiators

Abstract

A series of novel hetero-bifunctional linkers functionalised as ATRP initiators and protein and peptide-reactive agents has been prepared using standard synthetic techniques. A protein-based initiator has been applied to the initiation of living polymerisation in the synthesis of a novel bioconjugate. The linkers were designed based on the properties of polyethylene glycol and short alkyl chains coupled to either amine selective or thiol selective moieties for chemoselectivity, and bromoisobutyryl esters to facilitate atom transfer living polymerisation. The bi-functional linkers have also been coupled to short peptides based on the RGD bio-recognition sequence synthesised by standard solid phase peptide synthesis and the protein. Human Serum Albumin (HSA) using standard conditions to prepare peptide/protein-based ATRP initiators. Attempts at functionalising peptides with the N succinimidyl 4-(2-bromo-2- methylpropionyloxy) butanoate linker were unsuccessful. Model test of the protein based ATRP initiators in living polymerisation towards a novel strategy for bioconjugate synthesis was inconclusive as premature termination of the polymer chain was observed by MALDI analysis.