Self-complementary [[5'-d(G-C)4]2] and non-selfcomplementary oligonucleotides [5'-d(TAG GTC AAT ACT) x 3'-d(ATC CAG TTA TGA)] containing 7-(omega-aminoalkyn-1-yl)-7-deaza-2'-deoxyguanosines (1a-c) (1) and 7-deaza-2'-deoxyguanosine instead of dG were studied regarding their thermal stability as well as their phosphodiester hydrolysis by either 3' --> 5'- or 5' --> 3'-phosphodiesterase studied by MALDI-TOF MS.
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http://dx.doi.org/10.1081/NCN-120022843 | DOI Listing |
BMC Bioinformatics
January 2025
International Institute "Solution Chemistry of Advanced Materials and Technologies", ITMO University, Saint-Petersburg, Russian Federation, 191002.
Background: Deoxyribozymes or DNAzymes represent artificial short DNA sequences bearing many catalytic properties. In particular, DNAzymes able to cleave RNA sequences have a huge potential in gene therapy and sequence-specific analytic detection of disease markers. This activity is provided by catalytic cores able to perform site-specific hydrolysis of the phosphodiester bond of an RNA substrate.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, Canada T1K 3M4.
Despite the remarkable resistance of the nucleic acid phosphodiester backbone to degradation affording genetic stability, the P-O bond must be broken during DNA repair and RNA metabolism, among many other critical cellular processes. Nucleases are powerful enzymes that can enhance the uncatalyzed rate of phosphodiester bond cleavage by up to ∼10-fold. Despite the most well accepted hydrolysis mechanism involving two metals (M to activate a water nucleophile and M to stabilize the leaving group), experimental evidence suggests that some nucleases can use a single metal to facilitate the chemical step, a controversial concept in the literature.
View Article and Find Full Text PDFJ Biol Chem
November 2024
RNAcious Laboratory, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland. Electronic address:
Nucleases, that is, enzymes that catalyze the hydrolysis of phosphodiester bonds in nucleic acids, are essential tools in molecular biology and biotechnology. Staphylococcus aureus nuclease is particularly interesting due to its thermostability and Ca dependence, making it the prime choice for applications where nuclease modulation is critical, such as ribosome profiling in bacteria and halophilic archaea. The latter poses a technical and economical challenge: high salt reaction conditions are essential for maintaining ribosome integrity but negatively impact the micrococcal nuclease (MNase) activity, necessitating using large amounts of nuclease to achieve efficient cleavage.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for the hydrolysis of the phosphodiester bond on the 5' side of an apurinic/apyrimidinic site during base excision repair. Moreover, in DNA, this enzyme can recognize nucleotides containing such damaged bases as 5,6-dihydro-2'-deoxyuridine (DHU), 2'-deoxyuridine (dU), alpha-2'-deoxyadenosine (αA), and 1,6-ethenoadenosine (εA). Previously, by pulsed electron-electron double resonance spectroscopy and pre-steady-state kinetic analysis, we have revealed multistep DNA rearrangements during the formation of the catalytic complex.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Chemistry, Stanford University, Stanford, CA 94305.
The key first step in the oligomerization of monomers is to find an initiator, which is usually done by thermolysis or photolysis. We present a markedly different approach that initiates acid-catalyzed polymerization at the surface of water films or water droplets, which is the reactive phase during a wet-dry cycle in freshwater hot springs associated with subaerial volcanic landmasses. We apply this method to the oligomerization of different nucleic acids, a topic relevant to how it might be possible to go from simple nucleic acid monomers to long-chain polymers, a key step in forming the building blocks of life.
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