Further Investigations into Microwave Assisted Solid Phase Peptide Synthesis: Synthesis of Modified Peptides

摘要

In solid phase peptide synthesis (SPPS), while certain peptide sequences are synthesized relatively easily, some sequences are much more difficult. Efficient couplings occur within a fully solvated peptide-polymer matrix, where reagent penetration is rapid and unhindered. Sudden decreases in reaction rates and incomplete couplings have been attributed to peptide aggregation resulting in poor solvation [1]. Microwave energy represents a fast and efficient way to enhance both the deprotection and coupling reactions hindered by aggregation. The Nterminal amino group and peptide backbone are polar and they constantly try to align with the alternating electric field of the microwave, this helps in breaking up the chain aggregation. The application of microwave energy has proved to be a major enabling tool for enhancing slow and difficult chemical reactions [2], Unlike conventional heating, microwave energy direetly activates any molecule with a dipole moment and allows for rapid heating at the molecular level. Microwave assisted SPPS has been successfully applied to and shown useful for the synthesis of a range of difficult peptides [3]. Microwave peptide synthesis routinely shows substantial improvements in crude purity with reduced synthesis time compared to conventional SPPS. Previous studies have investigated the effects of microwave on aspartimide formation and epimerization, and offered optimized conditions for susceptible sequences to these wellknown side reactions [4]. We now report our recent results on the development of microwave assisted N-terminal modifications and head-to-tail on-resin cyclization.