Method and application of protein thermal stability measurement combined with bidirectional stable isotope labeling proteomics screening drug targets

Abstract

The invention discloses a method and application of protein thermal stability measurement combined with bidirectional stable isotope labeling proteomics screening drug targets. This method uses the quantitative method of forward-reverse isotope labeling combined with the measurement technology of protein thermal stability change, which can globally identify the target protein that interacts with the drug by observing which proteins in the cell undergo thermodynamic changes under the package of the drug . The method of the present invention overcomes the shortcomings of the high false positive rate of traditional identification methods, and has the characteristics of high throughput, high depth, high precision, wide detection range, and short time-consuming, breaking the limitations of the prior art in drug target identification It provides strong support for drug target research.

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.

Images