Boc-TOTA Polymer Particles for Oligonucleotide Synthesis
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Solution Overview
Problem
Current solid supports for oligonucleotide synthesis, such as those using aromatic amine monomers, face limitations including low reactivity, toxicity, and steric hindrance, which hinder efficient synthesis of long oligonucleotides and pose challenges in reproducibility and safety.
Innovation Solution
The development of porous cross-linked polymer particles incorporating an amine-containing acrylamide monomer, specifically Boc-TOTA, which allows for optimal spacing of oligonucleotides and improved accessibility of reactive groups, enhancing synthesis efficiency and yield while minimizing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If aromatic amine monomers are used in solid supports, then the support provides functional groups for coupling, but the reactivity is low and synthesis efficiency decreases
Solution Approach 1:
The patent changes the chemical parameters of the monomer from aromatic amine to acrylamide derivative, fundamentally altering the reactivity and coupling efficiency characteristics of the solid support
Solution Approach 2:
The patent creates a composite polymer structure incorporating acrylamide monomers with specific functional groups (Boc-TOTA) combined with cross-linking agents to achieve both high reactivity and structural stability
2Ease of manufacture
If aromatic amine monomers are used in solid supports, then the support provides coupling functionality, but toxicity increases
Solution Approach 1:
The patent employs a disposable solid support system where the acrylamide-based particles are designed for single-use in synthesis reactions, eliminating the need for repeated cleaning and reducing cumulative toxicity exposure
Solution Approach 2:
The patent uses composite polymer materials combining acrylamide monomers with specific functional groups that provide coupling functionality while being inherently less toxic than aromatic amine alternatives
3Ease of operation
If aromatic amine monomers are used in solid supports, then the support provides surface functional groups, but steric hindrance increases and accessibility of reactive groups decreases
Solution Approach 1:
The patent changes the spatial parameters of the functional groups by using acrylamide derivatives with specific molecular geometries that reduce steric bulk while maintaining coupling functionality
Solution Approach 2:
The patent creates localized regions of high functional group density on the particle surface while maintaining overall particle porosity, ensuring both high reactivity and good mass transfer
4Length of moving object
If long oligonucleotides are synthesized, then the product length increases, but synthesis yield decreases due to steric hindrance and low reactivity
Solution Approach 1:
The patent optimizes multiple parameters including monomer structure, particle porosity, and functional group density to enable efficient synthesis of long oligonucleotides with yields exceeding 90%
Solution Approach 2:
The patent employs highly porous solid support particles with optimized pore size distributions that facilitate mass transfer and reduce steric hindrance during synthesis of long oligonucleotide chains
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
The use of Boc-TOTA particles enables high-yield, high-quality synthesis of long oligonucleotides with reduced toxicity and improved reproducibility, suitable for large-scale industrial production.
Implementation Method 1
incorporating an amine-containing acrylamide monomer... allows for optimal spacing of oligonucleotides and improved accessibility of reactive groups
Data Source
Figure 1A(i)~1B
Figure 2A~2B
Figure 3A~3B
AI summary
This invention relates to polymer particles for solid phase oligonucleotide synthesis. The oligonucleotide may be linked to the particle via a linker having an amide- oligoethyleneglycol-amine structure. The particles may be considered to act as a solid support during the oligonucleotide synthesis. Also disclosed are processes for preparing such polymer particles, compositions and systems comprising such particles, and uses thereof.