Porous Polymeric Beads for Oligonucleotide Synthesis
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Solution Overview
Problem
Current polymeric solid supports for oligonucleotide synthesis, such as porous crosslinked phenolic polystyrene copolymer beads, are susceptible to oxidation and have drawbacks like reduced reactivity due to pendant vinyl groups and steric hindrance issues, limiting their loading capacity and efficiency, especially for longer oligonucleotides.
Innovation Solution
A novel copolymer comprising specific repeating units and crosslinker monomers is developed, which forms porous polymeric beads with improved loading capacity and stability, avoiding the use of divinylbenzene to mitigate oxidative issues and enhance mechanical integrity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If phenolic polystyrene copolymer beads are used as solid support, then reactive sites are available for nucleoside immobilization, but the beads are susceptible to oxidation by air
Solution Approach 1:
The patent changes the chemical composition parameters of the solid support by replacing phenolic groups with alternative functional groups that provide similar reactivity for nucleoside immobilization but exhibit reduced oxidation susceptibility, thereby maintaining reliability while reducing harm from oxidation
Solution Approach 2:
The patent employs composite material design by combining polystyrene with modified crosslinking agents or functional group substitutions that create a composite structure retaining the necessary reactive sites while incorporating oxidation-resistant components
2Strength
If DVB crosslinking is used to form porous beads, then mechanical integrity is improved, but pendant vinyl groups exhibit reduced reactivity and may participate in undesirable side reactions
Solution Approach 1:
The patent extracts or removes the problematic pendant vinyl groups from the crosslinked structure by using alternative crosslinking mechanisms or agents that do not generate these reactive side groups, thereby eliminating the source of undesirable side reactions while preserving mechanical integrity
Solution Approach 2:
The patent changes the crosslinking chemistry parameters by substituting DVB with alternative crosslinking agents or methods that achieve comparable mechanical strength without generating pendant vinyl groups, thus preventing harmful side reactions
3Quantity of substance
If high loading of nucleoside (350 μmol/g) is achieved on polystyrene supports, then large quantities of oligonucleotides can be synthesized, but steric hindrance between adjacent DNA chains reduces synthetic efficiency
Solution Approach 1:
The patent applies segmentation by designing a crosslinked structure that creates spatial separation or increased distance between adjacent nucleoside attachment sites, allowing high loading capacity while reducing steric hindrance through structural compartmentalization
Solution Approach 2:
The patent utilizes dimensional optimization by controlling the pore size distribution and three-dimensional architecture of the crosslinked network to provide adequate spatial separation in multiple dimensions, enabling high loading without compromising synthetic efficiency
Data Source
AI summary
Embodiments of the present application relate to porous polymeric beads solid support for use in oligonucleotide synthesis and the method of producing and using the same. Further embodiments relate to porous polymeric beads and method for preparing and using the same.