Method for identifying DNA (Deoxyribose Nucleic Acid) coded seedling compound capable of being cut off by operation
An identification method and compound technology, which are applied in the identification field of DNA-encoded seed compounds, and can solve problems such as inability to precisely locate
Pending Publication Date: 2022-07-19
HITGEN INC
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Problems solved by technology
Therefore, the DNA ends of intermediate products and by-products in DEL synthesis can still obtain complete DNA chain information through ligation, resulting in the final product, intermediate products and by-products of a certain DEL molecule in the synthesis route being labeled After obtaining the information of the same DNA sequence, after screening, sequencing and data analysis, the structure of the compound that binds to the target protein cannot be precisely located
Method used
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Embodiment 1
[0046] Example 1. Affinity screening of ROCK 2 protein to determine potential hits
[0047] 1) Following the synthesis strategy of DNA-encoded compound libraries, step-by-step synthesis of potential hits was performed on DNA with operable cleavage groups. The synthesized sample was filtered through a filter to obtain a purified sample. Dissolve the purified sample in H 2 A solution of 1.0 mmol per liter was prepared in O / DMSO (96:4), and then placed under a light condition of 365 nm at 0 degrees Celsius and a light intensity of 800 J for 40 minutes. The reaction solution was sampled for mass spectrometry monitoring to determine the conversion (80%) of the reaction.
[0048] The reaction solution was used for filter filtration, and the collected filtrate was the solution containing the potential hit compound.
[0049]
[0050] 2) Configuration of screening buffer: 50 mM Tris, 150 mM NaCl, 1 mM TCEP, 0.01% Tween20, pH 8.0; configuration of elution buffer: 50 mM Tris, 150 m...
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Abstract
The invention relates to an identification method of an operably-cleavable DNA (deoxyribonucleic acid) coded seedling compound, which comprises the following steps: screening and analyzing according to a DNA coded compound library to obtain a DNA seedling compound, carrying out resynthesis of a potential seedling compound on DNA with an operably-cleavable group according to a synthesis strategy of the DNA coded compound library, and releasing the seedling compound under specific conditions. Then carrying out affinity incubation with a target spot, and carrying out molecular identification on an eluate by utilizing mass spectrum, so as to accurately identify the seedling compound. According to the present invention, the accurate and rapid discovery of the DNA coding seedling compound can be achieved, and the influence of the DNA can be avoided through the operable cutting group.
Description
technical field [0001] The invention belongs to the field of drug screening, and in particular relates to an identification method for operably cut DNA-encoded hits based on liquid chromatography-mass spectrometry. Background technique [0002] DNA Encoded Library (DEL), as an important means for the discovery of new drug lead compounds, is gradually developing into an important driving force for drug discovery. The advantage of DEL is that it can complete the construction and screening of hundreds of millions or even tens of billions of molecular libraries in a short time and efficiently, showing time and cost advantages in new drug discovery (WO2005058479, WO2018166532, CN103882532). [0003] The traditional determination of DNA-encoded hits is based on the bioinformatics calculation of the screening enrichment value based on sequencing data, and then with reference to the synthesis history and the combination information corresponding to the corresponding molecular buildi...
Claims
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Patent Timeline
Login to View More IPC IPC(8): G01N30/02G01N30/06G01N30/72
CPCG01N30/02G01N30/06G01N30/72G01N2030/027
Inventor 李进甘易冯静刘观赛万金桥
Owner HITGEN INC