Solid Phase Oligonucleotide Synthesis

As oligonucleotide therapeutics continue to evolve and show promise in various research and clinical applications, manufacturers face the challenge of efficiently producing oligonucleotides with the required specificity and quality. Solid phase oligonucleotide synthesis (SPOS) has emerged as a key technology in this area, offering an automated, reliable approach to assembling oligonucleotides with precise sequences and modifications. This method enables the efficient production of oligonucleotides, significantly reducing the consumption of reagents.

Alfa Chemistry has extensive experience in the field of SPOS. We offer a specialized solid phase synthesis platform designed to meet the customized needs of different customers. Whether you need straightforward sequences or more complex, modified oligonucleotides, our SPOS technology is tailored to deliver the highest quality products for your specific requirements.

Advantages of Solid Phase Synthesis

The advantages of solid phase synthesis can be summarized as follows:

Firstly, large excesses of solution-phase reagents are used to drive reactions quickly to completion. After each step, there is no need for complex purification processes, as excess reagents and impurities are easily washed away.

Secondly, the entire solid-phase synthesis process is amenable to automation, especially using computer-controlled solid phase synthesizers, which significantly enhances efficiency and consistency.

In addition, solid-phase synthesis offers excellent scalability, enabling efficient production from gram to kilogram quantities, ensuring fast and high-yield synthesis on a large scale.

Solid Supports

Solid supports, often referred to as resins, play a crucial role in the synthesis of oligonucleotides. These insoluble particles, typically ranging from 50 to 200 μm in diameter, serve as the foundation to which oligonucleotides are attached during the synthesis process. Various types of solid supports have been utilized over the years, but controlled pore glass (CPG) and polystyrene have emerged as the most effective options.

• Controlled pore glass (CPG) offers the advantage of a porous structure, allowing for efficient access of reagents and solvents during synthesis while providing excellent mechanical stability. This makes CPG suitable for both small-scale and large-scale oligonucleotide production.
• Polystyrene, on the other hand, is favored for its cost-effectiveness and compatibility with various chemical reactions involved in oligonucleotide synthesis. It is well suited for efficient oligonucleotide synthesis, especially on a small scale (e.g. 40 nmol).

Overall, the choice of solid support significantly impacts the efficiency, yield, and quality of the synthesized oligonucleotides, making it a critical consideration in the synthesis process.

Solid Phase Phosphoramidite Chemistry

Solid phase phosphoramidite chemistry has been used for decades to synthesize oligonucleotides. Synthesis starts with deprotection of the 5'-hydroxyl group of the nucleoside attached to the solid support. This is followed by a coupling step with the addition of the phosphoramidite of the next nucleoside in the sequence and an activator, which is used to increase the reactivity of the phosphoramidite. An essential capping step comes next, which acetylates any unreacted 5'-hydroxyl groups from the coupling step, ensuring precise control over the oligonucleotide sequence. Finally, the phosphate is oxidized and once the final oligonucleotide is completely deprotected, a phosphodiester bond can be formed. This cycle of deprotection, coupling, capping, and oxidation is repeated until the desired oligonucleotide sequence is fully assembled.

Figure 1. The phosphoramidite synthesis cycle^[1].

Our products and services are for research use only and cannot be used for any clinical purposes.

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