Method for preparing screening spare library of natural product mixture medicament such as Chinese traditional medicine and application thereof

Abstract

The invention provides a preparation method of secondary metabolite mixture drug screening library for the drug screening based on protein crystal structure and the use of the drug screening library for screening drugs based on protein crystal structure. The preparation method is high in efficiency, rapid, accurate, reliable and practicable. By optimizing the raw medicines, the method avoids interference components and retains other components of the raw medicine. The inventive drug screening library helps to rapidly obtain a refined three-dimensional structure of a composite of target molecule and target protein.

Description

technical field [0001] The present invention relates to a method for preparing a drug screening candidate library and its application, more specifically, to a method for preparing a drug screening candidate library for a natural product mixture derived from traditional Chinese medicines, which is used for drug screening based on protein crystal structure and its application. Background technique [0002] Natural products, also known as secondary metabolites (Secondary Metabolites), have structural diversity and biological activity diversity. Natural products and their derivatives have played an unlimited role in the treatment of diseases in the past, and are also one of the most potential resources in the current drug development process (Newman DJ, GraggGM, Snader KM.Nat Prod Rep, 2000, 17( 3): 215-234; Lee K-H. J Nat Prod. 2004, 67(2): 273-283). However, in the past 10 years, the research interest of natural products in the pharmaceutical industry has declined, mainly du...

AI Technical Summary

Problems solved by technology

[0014] But this method also has its own limitations: first, the groups with smaller molecular weight are not easy to mix with the small molecules (such as DMSO) existing in the crystallization solution in the electron density of low resolution (resolution below 2.5 Ȧ). etc.), ions (such as acid radical ions, etc.), etc., so the crystal quality of the target protein is required to be high, which greatly limits the scope of the target protein; secondly, small molecules that can exist stably and have a molecular weight of 200Da The types of groups are limited, and there are only hundreds to thousands of components in the candidate libraries currently used for structural screening, which greatly limits the possibility of hits; again, this screening method will not be able to synthesize many , Natural products that cannot be decomposed into basic groups are excluded from the scope of drug screening, limiting the scope of screening

Not only is the process slow, inefficient, and labor-intensive, but there is also no guarantee that the compounds screened will be chemically feasible

Images