Progress in Chemical Synthesis of Peptides and Proteins

Wen Hou,Xiaohong Zhang,Chuan-Fa Liu

doi:10.1007/s12209-017-0068-8

Wen Hou, Xiaohong Zhang + Show 1 more

Open Access

https://doi.org/10.1007/s12209-017-0068-8

Copy DOI

Abstract

For the proteins that cannot be expressed exactly by cell expression technology (e.g., proteins with multiple posttranslational modifications or toxic proteins), chemical synthesis is an important substitute. Given the limited peptide length offered by solid-phase peptide synthesis invented by Professor Merrifield, peptide ligation plays a key role in long peptide or protein synthesis by ligating two small peptides to a long one. Moreover, high-molecular-weight proteins must be synthesized using two or more peptide ligation steps, and sequential peptide ligation is such an efficient way. In this paper, we reviewed the development of chemical protein synthesis, including solid-phase peptide synthesis, chemical ligation, and sequential chemical ligation.

Highlights

For the proteins that cannot be expressed exactly by cell expression technology (e.g., proteins with multiple posttranslational modifications or toxic proteins), chemical synthesis is an important substitute
For the proteins that cannot be expressed exactly by cell expression technology, chemical synthesis is an important substitute
Given the limited peptide length offered by solid-phase peptide synthesis invented by Professor Merrifield, peptide ligation plays a key role in long peptide or protein synthesis by ligating two small peptides to a long one

Summary

Introduction

For the proteins that cannot be expressed exactly by cell expression technology (e.g., proteins with multiple posttranslational modifications or toxic proteins), chemical synthesis is an important substitute. Small peptides are prepared by SPPS and coupled via chemical ligation (Fig. 4). The capture reaction is especially efficient for the 1,2-thiol amine moiety, as the aldehyde group selectively condenses with an N-terminal cysteine residue to form a stable thiazolidine intermediate.

Results

Conclusion