Amino Modifier Modification Service
Introduction
Amino modifiers are a cutting-edge chemical strategy in oligonucleotide engineering, introducing amino groups at specific positions of sugar moieties or nucleobases to enhance molecular interactions. These modifications address critical therapeutic challenges by improving target affinity through stronger Watson-Crick binding and stabilized duplex formation, enhancing biostability via nuclease resistance for prolonged in vivo half-life, and optimizing cellular uptake with charge-neutral or cationic modifications to overcome delivery barriers. Our services include custom synthesis of tailored amino-modified oligonucleotides using advanced phosphoramidite chemistry, analytical profiling with rigorous QC for purity, structural integrity and stability, and therapeutic development support from in silico design to preclinical validation. Partner with us to transform genetic targets into clinical breakthroughs.
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Amino Modifiers
Amino modifiers are a class of chemical reagents or modification strategies used in oligonucleotide engineering to introduce amino groups (-NH2). The core of this is to precisely link amino groups to specific positions of oligonucleotides (such as the 5'-end, 3'-end, internal sites, glycosides or nucleoside bases) through covalent bonds. This modification can retain the base pairing specificity necessary for targeted interactions while maintaining to achieve conjugate with fluorescent dyes, peptides or nanoparticles after synthesis, thereby endowing oligonucleotides with new functional properties.
Key Advantages
- Enhanced cellular uptake: Positively charged amines interact more strongly with negatively charged cell membranes, significantly enhancing the ability of oligonucleotides to enter cells.
- Controllable functionalization: Achieve precise and reliable connection of therapeutic agents, imaging agents or delivery carriers to ensure that each modification can play a specific role.
- Optimizing stability: Amino groups can act as a barrier against exonucleases, effectively prolonging the half-life of oligonucleotides in serum and enhancing their durability in biological environments.
- Multi-mode compatibility: Seamlessly adapted to various means such as PCR and antisense technology, providing flexible options for diverse research needs.
Design Considerations
The core of amino modifiers lies in introducing amino groups into oligonucleotides via chemical synthesis methods (e.g., phosphoramidite chemistry). This process involves several key elements:
- Modification positions: Amino groups can be introduced at the 5' end, 3' end, or internal sites of oligonucleotides (such as the 2' position of sugar rings or specific sites on nucleobases). Modifications at different positions are tailored to suit distinct application scenarios.
- Linkers: Amino groups are typically connected to oligonucleotides via linkers. Common types include carbon chain spacers (e.g., C3, C6, C12) and flexible chains containing PEG. The length and structure of these linkers influence amino group reactivity, steric hindrance, and interactions with other molecules.
- Chemical reagents: Key reagents for amino modification include amino-modified phosphoramidite monomers. These reagents are integrated into the oligonucleotide chain during solid-phase synthesis, ultimately yielding amino-functionalized oligonucleotides.
Workflow
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Sequence Optimization & Modification Design
Clients provide target sequences and conjugation requirements and our team designs modification sites linker types and density to align perfectly with functional goals This step ensures the amino modifications will enhance rather than hinder the oligonucleotide's intended performance
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Solid-Phase Synthesis
State-of-the-art synthesizers incorporate amino modifiers such as 5'-Amino-Modifier C6 using precise phosphoramidite chemistry each step achieving coupling efficiency above 99% to guarantee accurate and consistent amino group insertion throughout the oligonucleotide chain
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Post-Synthesis Conjugation (Optional)
Controlled conjugation of dyes peptides or lipids is performed via NHS ester or maleimide chemistry under inert conditions to prevent unwanted side reactions ensuring the conjugated molecules remain stable and functional
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Purification & QC
HPLC and MS analysis confirm sequence accuracy verify proper modification incorporation and ensure purity levels exceed 95% Additional stability assays testing serum and nuclease resistance validate the oligonucleotide's performance in biological environments
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Delivery
You receive customized oligos in either lyophilized form or buffer-suspended formats along with detailed reports that include modification sites molar extinction coefficients and comprehensive storage guidelines to maintain integrity
Timeline
The process takes 4 to 8 weeks depending on sequence length and the complexity of conjugation requirements with each stage optimized to balance speed and precision
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What We Can Offer?
Tailored Modification Strategies
Proprietary algorithms analyze sequence structure and functional goals to predict optimal modification sites ensuring each amino group placement maximizes conjugation efficiency and target binding.
Ultra-Pure Synthesis
Dual-HPLC purification processes rigorously remove diastereomer impurities and free modifiers resulting in consistently high purity that minimizes background interference in sensitive assays.
Scalability
Our production systems enable seamless transitions from small research-grade batches in the nmol range to large GMP-compliant productions at the kg scale with uniform quality across all volumes.
Rapid Turnaround
Parallelized production lines and optimized synthesis protocols cut timelines by 30% compared to standard methods delivering high-quality amino-modified oligos without compromising precision.
End-to-End Support
Our team provides comprehensive assistance from initial design and modification planning to in vitro and in vivo validation including expert troubleshooting for conjugation challenges throughout the project lifecycle.
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FAQs
Q1: How does amino modification affect oligonucleotide Tm values?
A: Internal amino modifications can slightly reduce Tm by 2-5°C due to minor distortion of the duplex structure caused by steric interference from the amine group and linker Terminal modifications on the other hand have negligible impact on Tm as they avoid direct disruption of base pairing interactions.
Q2: What linker length is optimal for amino-modified oligonucleotides used in protein conjugation?
A: For protein conjugation C6 or C12 linkers are generally optimal These longer spacers reduce steric hindrance between the oligonucleotide and protein allowing more efficient formation of stable amide bonds Short C3 linkers may limit conjugation efficiency with large proteins but work well for small molecules.
Q3: Can multiple amino groups be added to a single oligo?
A: Yes, multiple amino groups can be incorporated into a single oligonucleotide. However they must be spaced at least 3 bases apart to prevent charge driven aggregation that could disrupt target binding or cellular uptake Strategic placement also ensures each amine group remains accessible for conjugation.
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