Chemical synthesis of proteins using hydrazide intermediates

Yi-Chao Huang,Lei Liu,Ge-Min Fang

doi:10.1093/nsr/nwv072

Yi-Chao Huang, Lei Liu + Show 1 more

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https://doi.org/10.1093/nsr/nwv072

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Abstract

AbstractProtein chemical synthesis offers useful and otherwise-difficulty-to-obtain biomacromolecules for biological and pharmaceutical studies. Recently, the hydrazide chemistry has drawn attentions in this field as peptide or protein hydrazides can be used as key intermediates for different synthesis and modification purposes. Besides being a traditional bioorthogonal chemical handle, a hydrazide group can serve as a readily accessible precursor of a thioester. This strategy significantly improves the efficiency and scope of native chemical ligation for protein chemical synthesis. Here we review the chemical transformations of peptide or protein hydrazides and total/semi/enzymatic protein synthesis methods involving peptide or protein hydrazides. Several examples of protein chemical synthesis using peptide hydrazides as key intermediates are described.

Highlights

Several examples of protein chemical synthesis using peptide hydrazides as key intermediates are described
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, ChinaReceived 31 August 2015; Revised September 2015; Accepted September 2015Proteins play a central role in the cellular processes of living organisms
The hydrazide chemistry has drawn attentions in this field as peptide or protein hydrazides can be used as key intermediates for different synthesis and modification purposes

Summary

Introduction

Several examples of protein chemical synthesis using peptide hydrazides as key intermediates are described. Our own work in the field indicates that protein or peptide hydrazides are useful intermediates for protein chemical synthesis. We describe recent applications of protein or peptide hydrazides in protein chemistry, with an emphasis on hydrazide-based native chemical ligation (NCL). Peptide hydrazides are good thioester surrogates for total chemical protein synthesis and protein semisynthesis.

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