Oligonucleotide Modification Service
Oligonucleotide modification involves precise adjustments to nucleic acid structure, including sugar backbone, bases, linkers, and fluorophores. These changes augment stability, binding, and specificity, broadening applications across disciplines. Modified oligonucleotides are crucial in gene therapy, modulating expression, rectifying mutations, and targeting pathogenic sequences. Diagnostic use leverages them for precise genetic variants and pathogen identification. Additionally, these modified strands play pivotal roles in RNA interference, gene silencing, and aptamer-mediated drug delivery. Bridging fundamental research with practicality, oligonucleotide modification propels progress in personalized medicine, molecular biology, and biotechnology, fostering innovation across fields.
Fig.1 Common chemical modifications in antisense oligonucleotides. (Khan, et al., 2021)
Our service is founded on state-of-the-art solid-phase synthesis and advanced chemical conjugation techniques. We utilize a highly controlled, automated phosphoramidite chemistry workflow for the initial synthesis of the oligonucleotide chain. At specific points in the synthesis, or after the full sequence is complete, we introduce a variety of chemical modifications using specialized reagents and conjugation methods. These core technologies allow for the precise and reproducible incorporation of modifications at various positions, including the phosphate backbone, the sugar ring, the nucleobase, and at the 5' or 3' termini.
Based on oligonucleotide structure, CD BioGlyco has developed several oligonucleotide-based modification services for clients to study the optional application of oligonucleotide analogs. Besides oligonucleotide-based modification services, CD BioGlyco also offers Custom Oligonucleotide Synthesis Services and Nucleoside & Nucleotide Modification Services for the generation of a better custom research proposal for our clients.
Oligonucleotide base modifications alter nucleotide structure, enhancing binding specificity, stability, and function for applications including gene silencing and diagnostics.
Oligonucleotide linker modification changes connecting segments, influencing spatial arrangement and interactions.
Oligonucleotide fluorophore modification incorporates fluorescent molecules, enabling visualization and tracking of DNA/RNA, pivotal in imaging and molecular studies.
Our oligonucleotide modification service follows a refined workflow designed for precision and reliability, ensuring that every custom-modified oligonucleotide is delivered with the highest quality.
The oligonucleotide is synthesized on a solid support using an automated synthesizer. This process involves the stepwise addition of phosphoramidite monomers, building the oligonucleotide chain from 3' to 5'.
At the designated positions, custom modifications are introduced. This can involve using modified phosphoramidites during synthesis for base or sugar modifications or performing post-synthesis conjugation for labels and linkers at the termini.
Once synthesis and modification are complete, the oligonucleotide is cleaved from the solid support and undergoes a deprotection step to remove protecting groups. The crude product is then purified using methods such as HPLC or PAGE to isolate the full-length, modified oligonucleotide from truncated sequences and other impurities.
Every modified oligonucleotide undergoes rigorous quality control to verify its purity and identity. We use advanced analytical techniques, including mass spectrometry, to confirm the molecular weight and purity.
DOI.: 10.1093/nargab/lqae058
Journal: NAR Genomics and Bioinformatics
Published: 2024
IF: 2.8
Results: This study developed and validated new molecular dynamics force field parameters for phosphorothioate (PS)-modified therapeutic nucleic acids to enable accurate atomistic simulations. The authors derived parameters through quantum mechanical calculations on dimethyl phosphorothioate (DMPT), optimizing bond lengths, angles, and dihedral terms involving the sulfur atom. They validated these parameters in 2 μs MD simulations across three systems: PS-modified B-DNA, an RNA hairpin with a single-nucleotide bulge, and a DNA:RNA hybrid duplex. Comparative analyses with natural (phosphate-linked) counterparts revealed that PS modifications induced bimodal twist distributions in CpG steps of B-DNA and increased conformational flexibility in the bulged nucleotide of RNA, while showing minimal impact on the DNA:RNA hybrid structure. These findings highlight PS-backbone effects on nucleic acid dynamics relevant to antisense oligonucleotide design.
Our oligonucleotide modification enables precise tailoring of nucleic acid properties (e.g., nuclease resistance, binding affinity) for therapeutic and diagnostic research. To ensure a robust supply of high-purity molecular building blocks for these advanced modifications, we offer targeted Nucleoside Production Services:
CD BioGlyco provides custom oligonucleotide modification services for our clients, if you have any questions or require details information, please feel free to contact us.
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