Controlled In-Cell Generation of Active Palladium(0) Species for Bioorthogonal Decaging.

Owing to their bioorthogonality, transition metals have become very popular in the development of biocompatible bond-cleavage reactions. However, many approaches require design and synthesis of complex ligands or formulation of nanoparticles which often perform poorly in living cells. This work reports on a method for the generation of an active palladium species that triggers bond-cleaving reactions inside living cells. We utilized the water-soluble Na2 PdCl4 as a simple source of PdII which can be intracellularly reduced by sodium ascorbate to the active Pd0 species. Once generated, Pd0 triggers the cleavage of allyl ether and carbamate caging groups leading to the release of biologically active molecules. These findings do not only expand the toolbox of available bioorthogonal dissociative reactions but also provide an additional strategy for controlling the reactivity of Pd species involved in Pd-mediated bioorthogonal reactions.

A Platform for Site-Specific DNA-Antibody Bioconjugation by Using Benzoylacrylic-Labelled Oligonucleotides.

Many bioconjugation strategies for DNA oligonucleotides and antibodies suffer limitations, such as site-specificity, stoichiometry and hydrolytic instability of the conjugates, which makes them unsuitable for biological applications. Here, we report a new platform for the preparation of DNA-antibody bioconjugates with a simple benzoylacrylic acid pentafluorophenyl ester reagent. Benzoylacrylic-labelled oligonucleotides prepared with this reagent can be site-specifically conjugated to a range of proteins and antibodies through accessible cysteine residues. The homogeneity of the prepared DNA-antibody bioconjugates was confirmed by a new LC-MS protocol and the bioconjugate probes were used in fluorescence or super-resolution microscopy cell imaging experiments. This work demonstrates the versatility and robustness of our bioconjugation protocol that gives site-specific, well-defined and plasma-stable DNA-antibody bioconjugates for biological applications.

Sugar modified pyrimido[4,5-b]indole nucleosides: synthesis and antiviral activity.

Three types of sugar modified pyrimido[4,5-b]indole nucleosides (2'-deoxy-2'-fluororibo-, 2'-deoxy-2'-fluoroarabino- and arabinonucleosides) were synthesized by glycosylation of 4,6-dichloropyrimido[4,5-b]indole followed by modification of sugar moiety and introduction of substituents into position 4 by cross-coupling reactions or nucleophilic substitutions. Some 2'-fluororibo- and 2'-fluoroarabinonucleosides displayed interesting anti-HCV activities (IC50 = 1.6-20 µM) and the latter compounds also some anti-dengue activities (IC50 = 10.8-40 µM).