biostudies-literatureUnknown36(3)Kliuchnikov EWe combined circular dichroism (CD) and viscosity measurements with molecular dynamics (MD) simulations and classification and regression approaches to machine learning to characterize solution structures of 22-mer, 25-mer, and 30-mer peptide- (-GlyArg6) conjugated phosphorodiamidate morpholino oligonucleotides (PPMOs). PPMO molecules form non-canonical folded structures with 1.4- to 1.5-nm radius of gyration, 4-6 base pairs and 5-11 base stacks, characterized by -49 to -71 kcal/mol free energy of folding. The 4.5-6.1 cm³/g intrinsic viscosity and Huggins constant of 4.5-9.7 indicate PPMO-PPMO interactions at higher concentrations. The random-coil 3'-end conjugated -GlyArg₆ portion does not alter molecular properties of phosphorodiamidate morpholino oligonucleotide (PMolecular therapy. Nucleic acids102685https://www.ebi.ac.uk/biostudies/studies/S-EPMC12408397biostudies-literatureMolecular properties and intramolecular interactions of peptide-conjugated phosphorodiamidate morpholino oligonucleotides.PMC12408397Maksudov FPierson DBarsegov VChanda AKliuchnikov EMarx KAfalseMolecular properties and intramolecular interactions of peptide-conjugated phosphorodiamidate morpholino oligonucleotides.We combined circular dichroism (CD) and viscosity measurements with molecular dynamics (MD) simulations and classification and regression approaches to machine learning to characterize solution structures of 22-mer, 25-mer, and 30-mer peptide- (-GlyArg6) conjugated phosphorodiamidate morpholino oligonucleotides (PPMOs). PPMO molecules form non-canonical folded structures with 1.4- to 1.5-nm radius of gyration, 4-6 base pairs and 5-11 base stacks, characterized by -49 to -71 kcal/mol free energy of folding. The 4.5-6.1 cm³/g intrinsic viscosity and Huggins constant of 4.5-9.7 indicate PPMO-PPMO interactions at higher concentrations. The random-coil 3'-end conjugated -GlyArg₆ portion does not alter molecular properties of phosphorodiamidate morpholino oligonucleotide (P2025-01-01T00:00:00Z2025 Sep2026-06-03T02:52:42.269Z2026-04-23T03:12:50.814ZS-EPMC124083974091789510.1016/j.omtn.2025.102685