ArticleMolecular therapy. Nucleic acids2026
Kinetics, thermodynamics, and mechanisms of PMO interactions from computational molecular modeling.
Article in Molecular therapy. Nucleic acids, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Phosphorodiamidate morpholino oligonucleotides (PMOs) are a class of antisense oligonucleotides. While PMOs have enabled several nucleic acid therapeutics, their structural and energetic solution properties remain poorly understood. Using solution viscosity measurements combined with computational molecular modeling, we explored interactions of therapeutic 22-mer, 25-mer, and 30-mer PMOs in concentrated solutions. Self-association of PMO monomers involves non-specific interactions, is energetically favorable (with estimates of -32 to -67 kcal/mol interaction energies), and exhibits biphasic kinetics involving a fast phase of hydrophobic anchoring followed by a slower phase associated with optimization of intermolecular base pairing and stacking interactions. The final complexes possess broad self-association interfaces of ∼700-1,600 Å
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