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Method for fishing active small molecules from mixed combination chemical molecule library

A technology of chemical molecules and mixed combinations, which is applied in the direction of material analysis, scientific instruments, and material separation through optical means. The effect of small sample volume and small measurement interference

Active Publication Date: 2021-11-16
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There is a patent CN101339167A that uses biological mass spectrometry to screen small molecular compounds, but its separation system and pretreatment methods are very cumbersome, and it is difficult to obtain relatively pure free and bound complexes in recovery and dissociation solution

Method used

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  • Method for fishing active small molecules from mixed combination chemical molecule library
  • Method for fishing active small molecules from mixed combination chemical molecule library
  • Method for fishing active small molecules from mixed combination chemical molecule library

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1 establishes HRMS-SERS analytical technique combination method

[0030] 1.1 Preparation of probe material

[0031] Synthesis of silver nanoparticles: Take a 250mL three-neck flask and soak it in an acid tank overnight, take it out the next day, rinse it, and then wash it with water for injection three times to ensure that the wall is pure and free of impurities. Dry in the oven and cool to room temperature. Accurately weigh 0.018g of silver nitrate powder during this period, and carefully pour it into a three-necked flask. Add 100mL of ultrapure water, shake well, connect the condenser and set the temperature of the electric heating mantle to 100°C, stir and heat the solution to a slight boil, then quickly add 2mL of 1% sodium citrate solution immediately. Observe the color change of the solution: from light yellow to dark yellow, then to gray-green, no change in color is observed, slightly lower the temperature to 90°C, continue magnetic stirring, and mai...

Embodiment 2

[0047] Example 2 Surface Enhanced Raman Spectroscopy Detection

[0048] 1. Preparation of gold (silver) nanoparticles

[0049] 1.1 Preparation of gold nanoparticles

[0050] Gold nanoparticles (AuNPs): take a 250mL three-neck flask, wash it with aqua regia (1 part of concentrated nitric acid and 3 parts of concentrated hydrochloric acid), take it out the next day, rinse it, and then wash it with water for injection three times to ensure that the wall is pure and free of impurities . Dry in the oven and cool to room temperature. Add 2 mL of 1% HAuCl to the flask 4 Add water to 200mL, connect a condenser, heat to 150°C with an electric heating mantle, stir and heat to reflux until slightly boiling. Add 2mL of 1% sodium citrate, control the temperature, observe the color change, from light yellow to black (110°C-120°C), and then to red (90°C), lower the temperature to 90°C, and keep the temperature for 40min to obtain gold nanoparticles decentralized system.

[0051] 1.2 Pr...

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Abstract

The invention discloses a method for fishing and screening active monomer components or active component groups from a combinatorial chemical mixture library based on surface enhanced Raman spectroscopy combined with high resolution mass spectrometry (HRMS). An active component monomer or an active component group based on target protein is screened out from a small-molecule mixed compound group in a fishing manner by combining SERS and HRMS analysis technologies. The method is small in measurement interference, low in false positive, extremely small in required sample amount, strong in signal, high in sensitivity, simple and convenient to operate, capable of realizing high-throughput screening and reusable in compound library, and provides a new strategy for a targeted drug screening approach.

Description

technical field [0001] The invention belongs to the technical field of drug screening, and in particular relates to a method for fishing active small molecules from a mixed combinatorial chemical molecule library. Background technique [0002] In the process of new drug research and development, it is very important to find lead candidates with biological activity. Traditional lead compound selection methods are costly, time-consuming, and have a high risk of failure. [0003] Combinatorial chemistry is a subject that combines chemical synthesis, combination theory, computer-aided design and manipulators, and cleverly connects different building blocks according to the combination principle in a short period of time, and systematically connects repeatedly, thereby generating a large number of molecular diversity groups and forming a compound library. ), and then use the combinatorial principle to screen and optimize library components to obtain possible compound structures w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N21/65G01N30/06G01N30/88
CPCG01N21/658G01N30/06G01N30/88
Inventor 梁重阳项金宝徐抒平戴璐
Owner JILIN UNIV
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