Solid-Phase Support for Oligonucleotide Synthesis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional solid-phase supports for oligonucleotide synthesis, particularly those using porous resin beads, face challenges in synthesizing long chain and modified oligonucleotides with high purity and quantity, especially when the loading amount of the nucleoside linker is low, leading to decreased synthesizability.
Innovation Solution
A solid-phase support comprising a porous resin bead with a monovinyl monomer unit, a crosslinkable vinyl monomer unit, and a polyethylene glycol unit, where a cleavable linker with a carboxy group is bound to the resin bead via dehydration condensation, allowing for high synthetic efficiency even with low linker loading amounts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If the loading amount of nucleoside linker is decreased to synthesize long chain oligonucleotides, then the synthetic purity is improved, but the synthesizability (synthetic quantity) becomes lower than expected
Solution Approach 1:
The patent changes the chemical parameters of the solid-phase support by introducing a polyethylene glycol unit into the resin bead structure. This parameter change modifies the surface properties and microenvironment of the support, enabling high synthesizability even at low linker loading amounts (1-80 μmol/g), thus resolving the contradiction between purity and quantity
Solution Approach 2:
The patent creates a composite material by combining porous resin beads with polyethylene glycol units. This composite structure integrates the porous architecture for high surface area with the hydrophilic polyethylene glycol component that improves oligonucleotide attachment and synthesis efficiency, allowing simultaneous achievement of high purity and quantity
2Quantity of substance
If a porous resin bead is used as solid-phase support, then the quantity of oligonucleotide per weight of support is increased, but the synthesizability decreases when linker loading amount is reduced
Solution Approach 1:
The patent modifies the chemical composition parameters of the porous resin bead by incorporating polyethylene glycol units. This changes the surface chemistry and microenvironment, making the support more suitable for low-loading applications while maintaining high oligonucleotide quantity, thus resolving the contradiction between quantity and reliability
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 configuration enables the synthesis of long chain and modified oligonucleotides with high synthetic quantity and purity, improving efficiency compared to conventional porous resin beads.
Implementation Method 1
a polyethylene glycol unit... bound with a polyethylene glycol unit
Implementation Method 2
a cleavable linker loaded on its surface, the porous resin bead having a group capable of binding to a carboxy group by a dehydration condensation reaction
Data Source
AI summary
The present invention provides a solid-phase support for oligonucleotide synthesis for synthesizing long chain oligonucleotide, RNA oligonucleotide and modified oligonucleotide at high synthetic quantity and high purity with a low loading amount of a linker. Provided is a solid-phase support for oligonucleotide synthesis comprising a porous resin bead having a monovinyl monomer unit, a crosslinkable vinyl monomer unit and a polyethylene glycol unit and a cleavable linker loaded on its surface,the porous resin bead having a group capable of binding to a carboxy group by a dehydration condensation reaction on its surface, the cleavable linker having a carboxy group, wherein the carboxy group of the cleavable linker is bound to the group capable of binding to a carboxy group, by a dehydration condensation reaction, anda loading amount of the cleavable linker is 1 to 80 μmol/g relative to the weight of the porous resin bead.