A novel approach to the synthesis of oligodeoxyribonucleotide boranophosphates

Deoxyribonucleoside 3′-boranophosphate derivatives including adenine, cytosine, guanine, and thymine bases were synthesized in good yields by the use of a new boranophosphorylation reaction. The reaction was found to be effective for the formation of internucleotidic boranophosphate linkages

Synthesis and biological activity of artificial mRNA prepared with novel phosphorylating reagents

Though medicines that target mRNA are under active investigation, there has been little or no effort to develop mRNA itself as a medicine. Here, we report the synthesis of a 130-nt mRNA sequence encoding a 33-amino-acid peptide that includes the sequence of glucagon-like peptide-1, a peptide that stimulates glucose-dependent insulin secretion from the pancreas. The synthesis method used, which had previously been developed in our laboratory, was based on the use of 2-cyanoethoxymethyl as the 2′-hydroxy protecting group. We also developed novel, highly reactive phosphotriester pyrophosphorylating reagents to pyrophosphorylate the 5′-end of the 130-mer RNA in preparation for capping. We completed the synthesis of the artificial mRNA by the enzymatic addition of a 5′-cap and a 3′-poly(A) tail to the pyrophosphorylated 130-mer and showed that the resulting mRNA supported protein synthesis in a cell-free system and in whole cells. As far as we know, this is the first time that mRNA has been prepared from a chemically synthesized RNA sequence. As well as providing a research tool for the intracellular expression of peptides, the technology described here may be used for the production of mRNA for medical applications

Sample Hanes–Woolf plots describing translesional synthesis for the incorporation of dC or dA opposite OxodI or OxodG

<p><b>Copyright information:</b></p><p>Taken from "The effect of the 2-amino group of 7,8-dihydro-8-oxo-2′-deoxyguanosine on translesion synthesis and duplex stability"</p><p>Nucleic Acids Research 2005;33(5):1637-1643.</p><p>Published online 18 Mar 2005</p><p>PMCID:PMC1067523.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p> () dC opposite OxodI; () dA opposite OxodI; () dC opposite OxodG; and () dA opposite OxodG

Van't Hoff plot of UV-melting experiments for dodecamers prepared from –

<p><b>Copyright information:</b></p><p>Taken from "The effect of the 2-amino group of 7,8-dihydro-8-oxo-2′-deoxyguanosine on translesion synthesis and duplex stability"</p><p>Nucleic Acids Research 2005;33(5):1637-1643.</p><p>Published online 18 Mar 2005</p><p>PMCID:PMC1067523.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p

Structure of nucleotides 7,8-dihydro-8-oxo-2′-deoxyguanosine (OxodG), 7,8-dihydro-8-oxo-2′-deoxyinosine (OxodI) and 2′-deoxyinosine (dI)

<p><b>Copyright information:</b></p><p>Taken from "The effect of the 2-amino group of 7,8-dihydro-8-oxo-2′-deoxyguanosine on translesion synthesis and duplex stability"</p><p>Nucleic Acids Research 2005;33(5):1637-1643.</p><p>Published online 18 Mar 2005</p><p>PMCID:PMC1067523.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p

Synthesis of 2-pyridylthiophosphinic acids and 2-pyridylthiophosphonate monoesters via nucleophilic aromatic substitution

<p></p> <p>In this study, we developed a method for the synthesis of 2-pyridylthiophosphinic acids and 2-pyridylthiophosphonate monoesters using easily accessible starting materials, <i>H</i>-phosphinate and <i>H</i>-phosphonate esters and pyridine <i>N</i>-oxides. The <i>H</i>-phosphinate and <i>H</i>-phosphonate esters were sulfurized to give <i>H</i>-thiophosphinate and <i>H</i>-thiophosphonate esters. The pyridine <i>N</i>-oxides were converted into <i>N</i>-methoxypyridinium sulfonates, which were then used for nucleophilic aromatic substitution with the <i>H</i>-thiophosphinate/thiophosphonate esters to afford 2-pyridylthiophosphinate monoesters and 2-pyridylthiophosphonate diesters. Finally, alkaline hydrolysis and subsequent neutralization afforded various 2-pyridylthiophosphinic acids and 2-pyridylthiophosphonate monoesters in good yields. The structure of a 2-pyridylthiophosphonate monoester was determined using X-ray crystallographic analysis.</p

Serendipitous One-Step Synthesis of Cyclopentene Derivatives from 5′-Deoxy-5′-Heteroarylsulfonylnucleosides as Nucleoside-Derived Julia–Kocienski Reagents

A serendipitous one-step transformation of 5′-deoxy-5′-heteroarylsulfonylnucleosides into cyclopentene derivatives is reported. This unique transformation likely proceeds via a domino reaction initiated by α-deprotonation of the heteroaryl sulfone and subsequent elimination reaction to generate a nucleobase and an α,β-unsaturated sulfone that contains a formyl group. The Michael addition of the nucleobase to the α,β-unsaturated sulfone and subsequent intramolecular Julia–Kocienski reaction eventually generate the cyclopentene ring. Heteroarylthio and acylthio groups can be incorporated into the cyclopentene core in place of the nucleobase by conducting this reaction in the presence of a heteroarylthiol and a thiocarboxylic acid, respectively. Cis,cis-trisubstituted cyclopentene derivatives are obtained as a single stereoisomer from ribonucleoside-derived Julia–Kocienski sulfones