Target identification of natural medicine with chemical proteomics approach: probe synthesis, target fishing and protein identification

Xiao Chen,Jigang Wang,Nan Ma,Zhen Liang,Bo Zhu,Yin Kwan Wong,Yurou Shao,Jing Tian,Yutong Wang,Chang Zou

doi:10.1038/s41392-020-0186-y

Abstract

Natural products are an important source of new drugs for the treatment of various diseases. However, developing natural product-based new medicines through random moiety modification is a lengthy and costly process, due in part to the difficulties associated with comprehensively understanding the mechanism of action and the side effects. Identifying the protein targets of natural products is an effective strategy, but most medicines interact with multiple protein targets, which complicate this process. In recent years, an increasing number of researchers have begun to screen the target proteins of natural products with chemical proteomics approaches, which can provide a more comprehensive array of the protein targets of active small molecules in an unbiased manner. Typically, chemical proteomics experiments for target identification consist of two key steps: (1) chemical probe design and synthesis and (2) target fishing and identification. In recent decades, five different types of chemical proteomic probes and their respective target fishing methods have been developed to screen targets of molecules with different structures, and a variety of protein identification approaches have been invented. Presently, we will classify these chemical proteomics approaches, the application scopes and characteristics of the different types of chemical probes, the different protein identification methods, and the advantages and disadvantages of these strategies.

Highlights

Over the last 30 years, natural products have become an important source of new drugs to target various diseases.[1,2] In contrast to chemically synthesized drugs, drugs derived from natural products possess remarkable advantages in terms of structural novelty, biocompatibility and functional diversity, stemming from long-term natural selection-based optimizations in their evolution.[3]
AND OUTLOOK In the development of new natural medicines, target identification facilitates the determination of the mechanism of action (MOA) and side effects, accelerating this process from discovery to market
Along with the development of chemical biology and proteomics, the chemical proteomics approach has become a popular method in target identification of small active molecules, especially natural products, providing an important theoretical basis for novel natural medicine research and development

Summary

REVIEW ARTICLE OPEN

Target identification of natural medicine with chemical proteomics approach: probe synthesis, target fishing and protein identification. Identifying the protein targets of natural products is an effective strategy, but most medicines interact with multiple protein targets, which complicate this process. An increasing number of researchers have begun to screen the target proteins of natural products with chemical proteomics approaches, which can provide a more comprehensive array of the protein targets of active small molecules in an unbiased manner. Five different types of chemical proteomic probes and their respective target fishing methods have been developed to screen targets of molecules with different structures, and a variety of protein identification approaches have been invented. We will classify these chemical proteomics approaches, the application scopes and characteristics of the different types of chemical probes, the different protein identification methods, and the advantages and disadvantages of these strategies

1234567890();,: INTRODUCTION

Chemical proteomics is a postgenomic version of classical drug

Immobilized probe and validated the probe activity with in vitro biochemical

Although immobilized probes are easily synthesized and widely