Two new rapid procedures for the full deprotection of synthetic oligonucleotides has been developed. We have successfully used the mixture of ethanolamine and ethanol (1:1) or pure ethanolamine for deprotection of oligonucleotides, prepared by different methods. In the case of oligonucleotides prepared by commonly used beta-cyanoethyl phosphoramidite and H-phosphonates method deprotection takes half an hour at 70 degrees C. We have found also that mixture of hydrazine, ethanolamine and methanol (1:3:3, v/v/v) can serve as a very efficient reagent for deprotection of oligonucleotides, prepared by beta-cyanoethyl phosphoramidite method with isopropoxyacetyl protecting group for cytosine residues. In this case deprotection time is 12-17 min at room temperature.
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J Pharm Sci
January 2025
Ionis Pharmaceuticals, Inc., 2855 Gazelle Ct., Carlsbad, CA 92010. Electronic address:
Complexes formed between aluminum cluster molecules that adopt a Ɛ-Al-Keggin structure and antisense oligonucleotides were observed as new impurity peaks during drug product stability testing. The Ɛ-Al-Keggin molecules were determined to be artifacts of the analysis, originating from contact between antisense oligonucleotide drug product solution and aluminum weigh boats used to prepare the analytical sample solutions The presence of the Ɛ-Al-Keggin molecules was confirmed through synthesis of the Keggin molecule through an established route and subsequent spiking studies. Binding affinity studies revealed that the Ɛ-Al-Keggin bound to oligonucleotide sequences of various lengths (10 to 20 bases) and base compositions, though there is some evidence for preferential binding to 5-methylcytosine-containing sequences.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Currently, no drugs directly treat liver fibrosis. Previously, we have shown that treatment with miR-29a-3p improved liver fibrosis in a mouse model. To investigate the effectiveness of nucleic acid therapy at a lower dose, a modified nucleic acid was prepared based on miR-29a-3p.
View Article and Find Full Text PDFJ Sep Sci
January 2025
Chair of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University in Toruń, Toruń, Poland.
Oligonucleotides (ONs) are an increasingly popular category of molecules in the pharmaceutical landscape, particularly attractive for the treatment of genetic and rare diseases. However, analyzing these molecules presents significant challenges, due to their highly hydrophilic nature, multiple negative charges, and the presence of closely related impurities resulting from the complex solid-phase synthesis process. Ion pairing reverse-phase liquid chromatography (IP-RPLC) is the preferred technique for ONs analysis but is not ideal for mass spectrometry (MS) coupling.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer.
View Article and Find Full Text PDFSensors (Basel)
January 2025
Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, 72 Powstańców Wlkp. Al., 70-111 Szczecin, Poland.
Biosensors are transforming point-of-care diagnostics by simplifying the detection process and enabling rapid, accurate testing. This study introduces a novel, reusable biosensor designed for direct viral RNA detection from unfiltered saliva, targeting SARS-CoV-2. Unlike conventional methods requiring filtration, our biosensor leverages a unique electrode design that prevents interference from saliva debris, allowing precise measurements.
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