Behaviour of modified nucleosides, tRNA components, and their analogues has been studied in the internucleotide bond formation catalysed by ribonucleases of various substrate specificity, polynucleotide phosphorylases, and T4 RNA ligase and the results are summarised in this paper. Pseudouridine, dihydrouridine, ribothymidine, 5-methylcytidine, inosine, and 6-methyladenosine can participate in the reaction of internucleotide bond formation the presence of most ribonucleases used, viz. Pb2, Pcl2, Pb1, Pch1, C2, T1, pancreatic RNase. 3-Methylcytidine and 4-acetylcytidine form internucleotide bond (as phosphate acceptors) usually by means of guanyl-specific ribonucleases, whereas 1-methylandenosine is incorporated with ribonuclease Pel2. 7-Methylguanosine and 1-methylguynosine 2',3'-cyclophosphates can be used as phosphate donors in the presence of ribonuclease Pb2; in the similar enzymatic reaction 6-isopentenyladenosine is an uneffective acceptor.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position.
Int J Mol Sci
February 2024
Department of Physics, Novosibirsk State University, 2 Pirogov Str., Novosibirsk 630090, Russia.
Staudinger reaction on the solid phase between an electronodeficit organic azide, such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for the chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide, either with a free carboxy group or in the form of an activated ester such as pentafluorophenyl, 4-nitrophenyl, or pentafluorobenzyl, was used to introduce a carboxylic acid function to the terminal or internal internucleotidic phosphate of an oligonucleotide via the Staudinger reaction. A subsequent treatment with excess primary alkyl amine followed by the usual work-up, after prior activation with a suitable peptide coupling agent such as a uronium salt/1-hydroxybenzotriazole in the case of a free carboxyl, afforded amide-linked oligonucleotide conjugates in good yields including multiple conjugations of up to the exhaustive modification at each phosphate position for a weakly activated pentafluorobenzyl ester, whereas more strongly activated and, thus, more reactive aryl esters provided only single conjugations at the 5'-end.
View Article and Find Full Text PDFInternucleotidic bond formation using -phosphonamidate derivatives and acidic activators.
RSC Adv
October 2023
Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science 2641 Yamazaki, Noda Chiba 278-8510 Japan
We previously developed a synthesis method for oligodeoxynucleotides using -phosphonamidate derivatives as monomers. In this synthesis method, -phosphonamidate monomers having a heterocyclic amino group as a leaving group reacts with an alcohol to form an internucleotidic -phosphonate diester in pyridine without any additives upon heating. In this study, -phosphonamidate reacted to form an internucleotidic linkage in the presence of acidic activators at room temperature.
View Article and Find Full Text PDFSynthesis of phosphoramidate-linked DNA by a modified DNA polymerase.
Proc Natl Acad Sci U S A
March 2020
Department of Molecular Biology, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114;
All known polymerases copy genetic material by catalyzing phosphodiester bond formation. This highly conserved activity proceeds by a common mechanism, such that incorporated nucleoside analogs terminate chain elongation if the resulting primer strand lacks a terminal hydroxyl group. Even conservatively substituted 3'-amino nucleotides generally act as chain terminators, and no enzymatic pathway for their polymerization has yet been found.
View Article and Find Full Text PDFThe role of the Hint1 protein in the metabolism of phosphorothioate oligonucleotides drugs and prodrugs, and the release of HS under cellular conditions.
Biochem Pharmacol
May 2019
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz 91-063, Poland.
Phosphorothioate oligonucleotides (PS-oligos) containing sulfur atom attached in a nonbridging position to the phosphorus atom at one or more internucleotide bond(s) are often used in medicinal applications. Their hydrolysis in cellular media proceeds mainly from the 3'-end, resulting in the appearance of nucleoside 5'-O-phosphorothioates ((d)NMPS), whose further metabolism is poorly understood. We hypothesize that the enzyme responsible for (d)NMPS catabolism could be Hint1, an enzyme that belongs to the histidine triad (HIT) superfamily and is present in all organisms.
View Article and Find Full Text PDFThe Chemistry of the Noncanonical Cyclic Dinucleotide 2'3'-cGAMP and Its Analogs.
Handb Exp Pharmacol
October 2017
BIOLOG Life Science Institute, Forschungslabor und Biochemica-Vertrieb GmbH, Flughafendamm 9a, 28199, Bremen, Germany.
The cyclic dinucleotides (CDNs) cyclic diguanosine monophosphate (c-diGMP) and cyclic diadenosine monophosphate (c-diAMP) with two canonical 3'→5' internucleotide linkages are ubiquitous second messenger molecules in bacteria, regulating a multitude of physiological processes. Recently the noncanonical CDN cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) featuring a mixed linkage, which consists of a 2'→5' and a 3'→5' internucleotide bond, has been identified as a signaling molecule in metazoan species in late 2012. 2'3'-cGAMP formation is biocatalyzed by cGAMP synthase (cGAS) upon sensing of cytosolic double-stranded DNA (dsDNA) and functions as an endogenous inducer of innate immunity by directly binding to and activating the adaptor protein stimulator of interferon genes (STING).
View Article and Find Full Text PDFWant 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!