New methods for chemical protein synthesis

Abstract

Chemical protein synthesis is a useful tool to generate pure proteins which are otherwise difficult to obtain in sufficient amounts for structure and property analysis. Additionally, because of the precise and flexible nature of chemical synthesis, it allows for controllable variation of protein sequences, which is valuable for understanding the relationships between protein structure and function. Despite the usefulness of chemical protein synthesis, it has not been widely adopted as a tool for protein characterization, mainly because of the lack of general and efficient methods for the preparation and coupling of peptide fragments and for the folding of polypeptide chains. To address these issues, many new methods have recently been developed in the areas of solid-phase peptide synthesis, peptide fragment assembly, and protein folding. Here we review these recent technological advances and highlight the gaps needing to be addressed in future research.