The synthesis cycle, particularly in the context of oligonucleotide synthesis, involves a series of steps that are crucial for the stepwise addition of nucleotide residues to the growing chain until the desired sequence is assembled.

Steps of the Synthesis Cycle

De-blocking (Detritylation): The process begins with the removal of the DMT (dimethoxytrityl) protecting group from the first, solid-support-linked nucleoside. This step results in the solid support-bound oligonucleotide precursor bearing a free 5'-terminal hydroxyl group

Coupling: In this step, the free 5-OH of the first, solid-support-linked nucleoside https://dmleetherapy.com/2024/02/02/bmk-glycidate-bridging-the-world-of-ester-synthesis/ attacks the phosphorus of the incoming second nucleoside, displacing its diisopropylamino group. This results in the addition of a new nucleotide residue to the growing chain

Oxidation: The unstable phosphite triester formed during the coupling step is converted to a stable phosphate triester, allowing the next cycle to proceed. This step prepares the growing chain for the addition of the next nucleotide residue

Capping: After the oxidation step, solid-support-linked nucleosides with unreacted 5-OH are acetylated, preventing elongation of sequences with deletion mutations. Capping is performed to drive all water out, which would otherwise inhibit the next cycle of the reaction

Significance and Applications

The synthesis cycle is a critical process in the production of oligonucleotides, which have diverse applications in research, diagnostics, and therapeutics. The stepwise addition of nucleotide residues allows for the precise assembly of desired sequences, enabling the customization ofoligonucleotides for specific applications.

Relationship to Cell Cycle

The synthesis cycle in the context of oligonucleotide synthesis should not be confused with the S phase of the cell cycle, where DNA synthesis occurs. The synthesis cycle in oligonucleotide synthesis specifically refers to the steps involved in the stepwise addition of nucleotide residues to create oligonucleotides, while the S phase of the cell cycle involves the replication of DNA in eukaryotic cells