Solid-Phase DNA Encoding via Filtration Purification
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Solution Overview
Problem
Current methods for solid-phase synthesis of DNA encoded compound libraries are limited by poor solubility in organic solvents, complex purification processes, and restricted application to water-based systems, making them inefficient for synthesizing small molecule compounds and requiring high equipment investment.
Innovation Solution
A method involving a solid carrier, linker molecules, and specific reaction conditions, including the use of CPG, dichloromethane, and pyridine, to facilitate DNA encoding and purification through filtration and washing, enabling synthesis in organic solvents and expanding the scope of chemical reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional liquid-phase DNA encoding method is used, then DNA can be successfully encoded with compounds, but the reaction system is restricted to water-based systems with poor solubility in organic solvents
Solution Approach 1:
The patent changes the fundamental parameter of the reaction medium from aqueous to organic solvent system. By using organic solvents like dichloromethane, dimethylformamide, or dimethyl sulfoxide instead of water-based systems, the method enables reactions with water-sensitive compounds and improves solubility of organic molecules while maintaining DNA encoding capability through solid-phase synthesis on CPG carrier.
Solution Approach 2:
The patent introduces a solid carrier (controlled pore glass, CPG) as an intermediary support system. The CPG carrier with its porous structure and silanol groups serves as a mediator that allows DNA encoding to occur in organic solvent systems. The carrier provides anchoring points for DNA sequences while being compatible with organic solvents, thus bridging the gap between DNA stability and organic reaction compatibility.
2Manufacturing precision
If DNA encoding is performed in aqueous system, then encoding efficiency is maintained, but purification process becomes complex and time-consuming
Solution Approach 1:
The patent extracts the DNA-encoded compounds from the reaction mixture by taking advantage of the solid-phase nature of the synthesis. The CPG carrier with attached DNA-compound conjugates is filtered out from the organic solvent solution, separating the encoded products from excess reagents and byproducts. This simple filtration-based extraction eliminates complex purification steps required in liquid-phase methods.
Solution Approach 2:
The solid-phase synthesis system on CPG carrier performs self-service purification. The immobilized DNA-compound conjugates automatically remain on the solid carrier while unreacted materials and byproducts dissolve in the organic solvent and are removed by filtration. This self-cleaning effect occurs during the reaction process itself, eliminating the need for separate complex purification operations.
3Productivity
If solid-phase synthesis on CPG carrier is used, then synthesis efficiency increases and production cycle reduces, but equipment investment and operational costs change
Solution Approach 1:
The patent employs disposable CPG carrier beads that can be used for multiple synthesis cycles but are ultimately discarded after a reasonable number of uses. This approach eliminates the need for expensive, complex reusable equipment while maintaining high synthesis efficiency. The relatively low-cost CPG carriers replace costly automated liquid handling systems and sophisticated purification equipment, making the process more economically viable for industrial applications.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method significantly enhances synthesis efficiency, reduces production cycles by over 50%, increases the diversity and purity of small chemical molecules, and lowers costs, making it suitable for industrial applications.
Implementation Method 1
CPG (controlled pore glass) is a kind of solid carrier which has silanol groups on the surface and inside the pores
Implementation Method 2
The forces between solid carrier and DNA mainly come from ion-ion interaction
Implementation Method 3
reacting a solid carrier G-1 with a linker molecule L-1, separating, purifying and obtaining L-G-1
Implementation Method 4
A method involving a solid carrier, linker molecules, and specific reaction conditions, including the use of CPG, dichloromethane, and pyridine, to facilitate DNA encoding and purification
Implementation Method 5
purification through filtration and washing
Data Source
AI summary
The present invention provides a method of solid-phase synthesis of DNA-encoded compound library. The method includes following steps: a) reacting solid carrier G-1 with linker molecule L-1 to prepare L-G-1; b) reacting DNA with linker molecule L-0 to prepare L-2; c) reacting L-G-1 with L-2 to prepare L-G-2; d) removing protection group of the L-G-2 and obtaining L-G-2-1; e) reacting the L-G-2-1 with synthetic building block and performing DNA encoding; and f) removing the solid carrier and obtaining the DNA-encoded compound library. Compared with the prior art, the present invention can complete post-treatment purification of the reaction only by filtration and irrigation processes for several times. The present invention is simple to operate, can shorten the production cycle of DNA encoded compound library with more than 50%, significantly increases the production efficiency and the unicity as well as the purity of the final products. Besides, the present invention has a high economic value, which is suitable for industrial application.