PMO

PMO monomers, specifically phosphorodiamidate morpholino (PDM) monomers, play a vital role in the synthesis of oligonucleotides called phosphorodiamidate morpholino oligonucleotides (PMOs). PMOs are a class of antisense therapeutic agents that bind to target RNA molecules and modulate gene expression. Here's a breakdown of how PMO monomers are applied in oligo synthesis:

Function:

• PMO monomers act as the building blocks for PMO oligonucleotides.

• Each PMO monomer contains a morpholino ring, a linker group, and a phosphoramidate moiety.

• The morpholino ring specifically recognizes and binds to complementary RNA sequences.

• The linker group connects the morpholino ring to the phosphoramidate moiety.

• The phosphoramidate moiety plays a crucial role in linking individual PMO monomers during oligo synthesis.

Process:

• PMO synthesis typically employs a solid-phase approach similar to DNA synthesis.

• A controlled sequence of PMO monomers is attached to a solid support one by one.

• Techniques like Fmoc (Fluorenylmethoxycarbonyl) or trityl chemistry are used to protect and deprotect functional groups on the monomers during the coupling process.

• After chain assembly, the PMO oligonucleotide is cleaved from the solid support and deprotected to obtain the final product.

Advantages of PMO Monomers:

Compared to traditional DNA oligonucleotides, PMO oligonucleotides made with PMO monomers offer several advantages:

• Increased stability: PMO backbone is more resistant to enzymatic degradation by nucleases.

• Improved binding affinity: PMO oligonucleotides can exhibit higher binding affinity towards target RNA.

• Reduced toxicity: PMO oligonucleotides generally demonstrate lower off-target effects and toxicity compared to DNA counterparts.

Challenges and Future Directions:

Although PMO monomers offer numerous benefits, there are ongoing efforts to improve PMO synthesis:

• Optimizing deprotection and coupling methods for higher efficiency.

• Developing new PMO chemistries compatible with automated synthesizers for faster and more scalable production.

• Creating new PMO conjugates with improved delivery properties.

Overall, PMO monomers are a critical component in the synthesis of PMO oligonucleotides, a promising class of therapeutic agents with the potential to treat various diseases.