Pseudo-Solid Support Protecting Group for Oligonucleotide Purification
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Solution Overview
Problem
Existing oligonucleotide synthesis methods, both solid-phase and liquid-phase, face challenges in scalability and efficiency, particularly in the liquid-phase method where purification steps are complex and yield is low.
Innovation Solution
A novel pseudo-solid-phase protecting group characterized by a benzoyl group substituted with an alkenyloxy group on the benzene ring and a carboxy group at the terminal, used in liquid-phase oligonucleotide synthesis, which simplifies purification and enhances reaction efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If liquid-phase synthesis method is used, then flexibility and customization are improved, but purification complexity increases and yield decreases
Solution Approach 1:
The patent introduces a pseudo-solid-phase protecting group as an intermediary substance that mediates between liquid-phase synthesis flexibility and solid-phase-like ease of purification. The protecting group temporarily binds to the oligonucleotide during synthesis, enabling simple filtration-based purification without complex chromatography steps, thus resolving the contradiction between synthesis flexibility and purification complexity
Solution Approach 2:
The patent changes the physical state parameter of the protecting group from solid-phase (immobilized on support) to pseudo-solid-phase (soluble but forms precipitates or aggregates), allowing the reaction to proceed in liquid phase while enabling easy separation through filtration or centrifitation, thereby improving both flexibility and simplifying purification
2Adaptability or versatility
If liquid-phase synthesis method is used, then flexibility and customization are improved, but synthesis speed decreases
Solution Approach 1:
The pseudo-solid-phase protecting group acts as a mediator that enables rapid purification through simple filtration, eliminating time-consuming chromatography steps. This intermediary approach allows the synthesis to maintain liquid-phase flexibility while achieving synthesis speeds comparable to or faster than solid-phase methods
Solution Approach 2:
The patent skips the complex purification steps traditionally required in liquid-phase synthesis by using the pseudo-solid-phase protecting group approach. The protecting group allows direct filtration to remove impurities, rushing through the purification process in minutes rather than hours, thus improving synthesis speed while maintaining flexibility
3Ease of manufacture
If conventional protecting groups are used, then synthesis is simpler, but purification steps cannot be omitted and reaction efficiency is low
Solution Approach 1:
The patent changes the solubility parameter of the protecting group to create a pseudo-solid-phase system. The protecting group is designed to be soluble during synthesis reactions but forms precipitates or aggregates under specific conditions (such as addition of non-solvents or pH adjustment), enabling simple filtration-based purification. This parameter change allows omission of complex purification steps while maintaining synthesis simplicity and improving reaction efficiency
Data Source
AI summary
The present invention aims to provide a novel pseudo-solid support protecting group that can be used for oligonucleotide synthesis by a liquid-phase method. The present invention also aims to provide a method for synthesizing oligonucleotides using the novel pseudo-solid support protecting group. According to the present invention, there is provided a compound represented by the following formula (1): (wherein R represents an alkenyl group having 14 to 60 carbon atoms, n represents 2 or 3, m represents 0 or 1, p represents 1 or 2, X represents C, N, O, or S, Y represents a single bond, B(CH2)t* or may form a ring together with X, and Z represents a single bond or (CH2)s (s is an integer of 1 to 5)). The present invention also provides a method for producing oligonucleotides using the compound.