Method and application for screening drug targets through combination of protein thermal stability testing and bidirectional stable isotope labeling proteomics

Abstract

The invention discloses a method and application for screening drug targets through combination of the protein thermal stability testing and the bidirectional stable isotope labeling proteomics. According to the method, the forward-reverse isotope labeling quantitative method is combined with the protein thermal stability testing technology, and proteins in cells have thermodynamic change under coating of drugs can be observed, thereby assisting in overall identifying target proteins in interaction with the drugs. The method overcomes the defect of high false positive rate of the conventionalidentifying methods, has the advantages of high throughput, high depth, high precision, wide detection range and short time consuming, breaks the limit of the prior art in the terms of identifying ofthe drug targets, and provides powerful support to research on the drug targets.

Description

technical field [0001] The invention belongs to the field of drug target protein screening, in particular to a method and application of protein thermal stability measurement combined with bidirectional stable isotope labeling proteomics screening drug targets. Background technique [0002] The specific binding of small molecule drugs to target proteins under physiological conditions (Drug Target Interaction) is the key to the successful treatment of diseases. Identifying the specific target protein of the drug and analyzing the molecular mechanism of the drug are important tasks throughout all stages of drug development, and are also the core content of drug preclinical research. However, under physiological conditions, a single small-molecule drug may have multiple target proteins in vivo, so a comprehensive identification of binding proteins of small-molecule drugs is helpful for the promotion of clinical application of drugs and the evaluation of their side effects. [...

AI Technical Summary

Problems solved by technology

[0006] Due to the small detection range and low detection accuracy of the existing technology in the search for small molecule drug targets, a variety of potential target proteins cannot be presented globally, which brings great difficulties to later experimental verification. It is very necessary to find a A high-throughput, high-precision drug target identification method

But so far, in the field of identifying the target protein of a specific small molecule drug, no research team has used the protein thermal stability change measurement technology combined with the quantitative proteomics of forward-reverse isotope labeling.

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