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Synthesis of multivalent fatty acid-conjugated antisense oligonucleotides: Cell internalization, physical properties, and in vitro and in vivo activities.
Bioorg Med Chem
March 2023
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:
Herein, we describe the design and synthesis of multi-conjugatable fatty acid monomer phosphoramidites and their conjugation to antisense oligonucleotides (ASOs). Multivalent long-chain fatty acid conjugation improved the cellular uptake of ASOs but decreased in vitro activity due to alterations in physical properties and cellular localization. In addition, multivalently fatty acid-conjugated ASOs showed different organ specificity compared with that of unconjugated ASO in in vivo experiment.
View Article and Find Full Text PDFPurification and functional properties of the membrane fissioning protein CtBP3/BARS.
Methods Enzymol
March 2006
Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
The fissioning protein CtBP3/BARS is a member of the CtBP transcription corepressor family of proteins. The characterization of this fissioning activity of CtBP3/BARS in both isolated Golgi membranes and in intact cells has indicated that the CtBP family includes multifunctional proteins that can act both in the nucleus and in the cytoplasm. The fissiogenic activity of CtBP3/BARS has a role in the fragmentation of the Golgi complex during mitosis and during intracellular membrane transport.
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