Application and Screening Method of Small Molecule Covalent Inhibitors in the Preparation of Drugs Inhibiting S-adenosylmethionine Decarboxylase

A technology of covalent inhibition of adenosylmethionine decarboxylase, which is applied in the field of biomedicine, can solve problems such as covalent group deviation, and achieve the effects of accelerated screening, wide applicability, and simple operation
CN106389403BActive Publication Date: 2019-02-19CHINA THREE GORGES UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
CHINA THREE GORGES UNIV
Publication Date
2019-02-19

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Abstract

The invention belongs to the field of bio-medicine, and in particular relates to an application of a small-molecule covalent inhibitor in preparing a medicine for inhibiting S-adenosylmethionine decarboxylase and a screening method. The structural formula of the small-molecule covalent inhibitor is as shown in Description, wherein R1 represents phenyl or aniline or benzamide or a substituted phenyl group thereof, methyl or ethyl or furan and a substituted group thereof, pyrrole and a substituted group thereof, pyridine and a substituted group thereof and the like; and the inhibitor further consists of pharmaceutically acceptable salt with a chemical structure shown as general formula I. A method for screening the small-molecule covalent inhibitor of the S-adenosylmethionine decarboxylase comprises the following steps: deleting pyruvoyl 68 residue in an S-adenosylmethionine decarboxylase crystal structure, and conducting optimizing in Rosetta software so as to obtain an optimized protein crystal structure; and conducting docking calculation on the optimized protein crystal structure and a searched small-molecule structure by virtue of AutoDockVina software, and screening calculating results in accordance with a grading order so as to obtain the small-molecule covalent inhibitor.
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Description

technical field

[0001] The invention belongs to the field of biomedicine, and in particular relates to the application and screening method of small molecule covalent inhibitors in the preparation of drugs inhibiting S-adenosylmethionine decarboxylase. Background technique

[0002] For a long time, in clinical and basic research, small molecular compounds have been widely used as drugs or regulatory molecules to treat diseases or study biological systems. These small molecular compounds can bind to target proteins in a covalent or non-covalent manner. However, covalent compounds were usually avoided in past rational drug screening and design because early researchers worried that covalent compounds would have large "off-target" effects and cause large side effects. Because of this, the past computer-aided screening methods were basically optimized for the docking of non-covalent compounds for screening, design, optimization and evaluation of the binding of non-covalent comp...

Claims

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