A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position.

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.

Activity of nsp14 Exonuclease from SARS-CoV-2 towards RNAs with Modified 3'-Termini.

The COVID-19 pandemic has shown the urgent need for new treatments for coronavirus infections. Nucleoside analogs were successfully used to inhibit replication of some viruses through the incorporation into the growing DNA or RNA chain. However, the replicative machinery of coronaviruses contains nsp14, a non-structural protein with a 3'→5'-exonuclease activity that removes misincorporated and modified nucleotides from the 3' end of the growing RNA chain.

[New Zwitter-Ionic Oligonucleotides: Preparation and Complementary Binding].

New zwitter-ionic oligonucleotide derivatives containing 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl phosphoramidate group are described. Automated synthesis of these compounds was carried out according to the β-cyanoethyl phosphoramidite scheme via the Staudinger reaction between 2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl azide and phosphite triester within oligonucleotide grafted to polymer support. 1,2,3,4-Tetrahydroisoquinoline-7-sulfonyl phosphoramidate group (THIQ) was stable under the conditions of standard oligonucleotide synthesis, including the removal of protective groups and cleavage of the oligonucleotide from the polymer support by treatment with a mixture of concentrated aqueous solutions of ammonia and methylamine (1 : 1) at 55°C.

Chiral -Symmetric Diimines with 4,5-Diazafluorene Units.

A synthetic approach to a new group of stable chiral -symmetric diimines with the 4,5-diazafluorene core has been developed based on condensation of dipinodiazafluorene with aromatic diamines. The chemical structures of new compounds were proven by spectroscopic methods and X-ray crystallography. All the compounds form solvates with organic solvents (chloroform, benzene, 1,4-dioxane) and water.

Phase transitions in the crystals of L- and DL-cysteine on cooling: the role of the hydrogen-bond distortions and the side-chain motions. 2. DL-cysteine.

Structural strain and a first-order phase transition in the crystalline DL-cysteine on cooling and on reverse heating were followed by Raman spectroscopy and X-ray diffraction. The transition is reversible and has a large hysteresis (over 100 K). The temperature at which the transition is observed depends strongly on the cooling/heating rate.