Large-scale synthesis of oligoribonucleotides has been performed successfully on a solid support by the phosphoramidite approach using levulinyl and tetrahydrofuranyl protection for the 5'- and 2'-hydroxyl groups respectively. A hexamer containing inosine and four fragments of a hammerhead-type ribozyme have been synthesized on a 10 mumol scale for structural studies by NMR spectroscopy and X-ray crystallography.
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Biochemistry
October 2024
Redona Therapeutics (formerly Twentyeight-Seven Therapeutics), 490 Arsenal Way, Watertown, Massachusetts 02472, United States.
Oligoadenylate synthetase 1 (OAS1) catalyzes the dsRNA-dependent polymerization of ATP to form oligoadenylate, a second messenger of the innate immunity system. This paper reports kinetic and mechanistic studies of OAS1-catalyzed dimerization of ATP to form 2'-5'-diadenylate and pyrophosphate (PP), the first step in ATP polymerization. Major findings include the following: (1) Reaction progress curves for the production of PP are biphasic, characterized by a presteady-state lag followed by the linear, steady-state production of PP.
View Article and Find Full Text PDFNucleic Acids Res
September 2024
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
The type III-A (Csm) CRISPR-Cas systems are multi-subunit and multipronged prokaryotic enzymes in guarding the hosts against viral invaders. Beyond cleaving activator RNA transcripts, Csm confers two additional activities: shredding single-stranded DNA and synthesizing cyclic oligoadenylates (cOAs) by the Cas10 subunit. Known Cas10 enzymes exhibit a fascinating diversity in cOA production.
View Article and Find Full Text PDFNucleic Acids Res
August 2024
College of Chemistry, Fuzhou University, Fuzhou 350108, China.
In the type III CRISPR system, cyclic oligoadenylate (cOA) molecules act as second messengers, activating various promiscuous ancillary nucleases that indiscriminately degrade host and viral DNA/RNA. Conversely, ring nucleases, by specifically cleaving cOA molecules, function as off-switches to protect host cells from dormancy or death, and allow viruses to counteract immune responses. The fusion protein Csx1-Crn2, combining host ribonuclease with viral ring nuclease, represents a unique self-limiting ribonuclease family.
View Article and Find Full Text PDFChemistry
July 2024
IBMM, Université de Montpellier, CNRS, ENSCM, 1919 route de Mende, 34293, Montpellier Cedex 5, France.
Peptide-oligonucleotide conjugates (POCs) are covalent architectures composed of a DNA or RNA molecules linked to a peptide. These constructs have found widespread applications ranging from hybrid nanomaterials to gene-targeted therapies. Considering the important role of POCs, a new catalytic approach for their preparation is reported here, that could be applied either on solid support in anhydrous media, or post-synthetically in aqueous buffer.
View Article and Find Full Text PDFAnnu Rev Anal Chem (Palo Alto Calif)
July 2024
Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA; email:
Ribonucleic acids (RNAs) are key biomolecules responsible for the transmission of genetic information, the synthesis of proteins, and modulation of many biochemical processes. They are also often the key components of viruses. Synthetic RNAs or oligoribonucleotides are becoming more widely used as therapeutics.
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