Successful syntheses of chlorophosphoramidate morpholino monomers containing tricyclic cytosine analogs phenoxazine, G-clamp, and G-clamp were accomplished. These modified monomers were incorporated into 12-mer oligonucleotides using trityl-chemistry by an automated synthesizer. The resulting phosphorodiamidate morpholino oligomers, containing a single G-clamp, demonstrated notably higher affinity for complementary RNA and DNA compared to the unmodified oligomers under neutral and acidic conditions. The duplexes of RNA and DNA with G-clamp-modified oligomers adopt a B-type helical conformation, as evidenced by CD-spectra and show excellent base recognition properties. Binding affinities were sequence and position dependent.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.joc.3c01658 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The international symposium ASOBIOTICS 2024 brought together scientists across disciplines to discuss the challenges of advancing antibacterial antisense oligomers (ASOs) from basic research to clinical application. Hosted by the Helmholtz Institute for RNA-based Infection Research (HIRI) in Wurzburg, Germany, on September 12-13th, 2024, the event featured presentations covering major milestones and current challenges of this antimicrobial technology and its applications against pathogens, commensals, and bacterial viruses. General design principles and modification of ASOs based on peptide nucleic acid (PNA) or phosphorodiamidate-morpholino-oligomer (PMO) chemistry, promising cellular RNA targets, new delivery technologies, as well as putative resistance mechanisms were discussed.
View Article and Find Full Text PDFPhase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy.
Cell Rep Med
January 2025
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8502, Japan. Electronic address:
Duchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, leading to dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping offers potential by partially restoring dystrophin, though current therapies remain mutation specific with limited efficacy. To overcome those limitations, we developed brogidirsen, a dual-targeting ASO composed of two directly connected 12-mer sequences targeting exon 44 using phosphorodiamidate morpholino oligomers.
View Article and Find Full Text PDFSex determination factor, a novel male-linked gene in the sea cucumber Apostichopus japonicus: Molecular characterization, expression patterns and effects of gene knockdown.
Comp Biochem Physiol B Biochem Mol Biol
January 2025
Key Laboratory of Mariculture& Stock Enhancement in North China's Sea, Ministry of Agriculture and Rural Affairs, Dalian Ocean University, Dalian 116023, China.
Apostichopus japonicus is a highly significant marine aquaculture species. Research findings have indicated that male sea cucumbers demonstrate a more rapid growth rate compared to females, underscoring the potential advantages of establishing an all-male population. In this study, we identified a specific protein-coding gene (ORFan) within a 4565 bp male fragment and named it sex determination factor (sdf).
View Article and Find Full Text PDFis essential for zebrafish embryogenesis and pronephros formation.
Front Cell Dev Biol
December 2024
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, United States.
Background And Objectives: Friedreich's Ataxia (FRDA) is a genetic disease that affects a variety of different tissues. The disease is caused by a mutation in the gene ( which is important for the synthesis of iron-sulfur clusters. The primary pathologies of FRDA are loss of motor control and cardiomyopathy.
View Article and Find Full Text PDFUnveiling the Role of TMPRSS2 in the Proteolytic Activation of Pandemic and Zoonotic Influenza Viruses and Coronaviruses in Human Airway Cells.
Viruses
November 2024
Institute of Virology, Philipps-University Marburg, 35043 Marburg, Germany.
Article Synopsis
- The zoonotic transmission of influenza A viruses (IAVs) and coronaviruses (CoVs) can lead to severe diseases, and the cleavage of glycoproteins is essential for their infectivity.
- The study focused on the role of transmembrane serine protease 2 (TMPRSS2) in cleaving viral proteins in human airway cells and its dependency for different IAV and CoV strains.
- Results showed that while TMPRSS2 is crucial for the activation of certain viruses like H1N1/1918 and MERS-CoV, others like SARS-CoV and some IAV subtypes show less dependency, indicating the potential for alternative proteases and highlighting TMPRSS2 as
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!