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Ruthenium(ii) polyazaaromatic complexes have gained interest in recent decades as biomolecular tools, especially in the development of new phototherapeutic agents. These light emissive Ru complexes based on π-deficient ligands were first designed to allow a photo-induced electron transfer (PET) with the guanine base in DNA since their 3MLCT state is highly photo-oxidizing. Later the field of research was extended to proteins with the highlighting of a PET process with the tryptophan residue. This paper reports the kinetics of the luminescence quenching of [Ru(TAP)2phen]2+ by several selected peptide sequences containing at least one tryptophan residue. By using a peptide library we highlight the important parameters influencing the kinetics of the photo-electron transfer process, such as the net electrostatic charge and the number of tryptophan residues. The best peptide candidates were selected to study the formation of photo-products by MALDI-ToF mass spectrometry. A high photoreactivity of the [Ru(TAP)2phen]2+ complex was observed and multiple photoadducts were characterized, among them inter-peptidic adducts as well as intra-peptidic adducts. [ABSTRACT FROM AUTHOR]

The conjugation of oligonucleotides with reporters is of great interest for improving their intrinsic properties or endowing new ones. In this context, we report herein a new procedure for the bis-labelling of oligonucleotides through oxime ligation (Click-O) and copper(I)-catalyzed alkyne-azide cycloaddition (Click-H). 5′-Azido and 3′-aldehyde precursors were incorporated into oligonucleotides, and subsequent coupling reactions through Click-O and Click-H (or vice versa) were successfully achieved. In particular, we exhaustively investigated the full compatibility of each required step for both tethering strategies. The results demonstrate that click Huisgen and click oxime reactions are fully compatible. However, whilst both approaches can deliver the targeted doubly conjugated oligonucleotide, the route involving click oxime ligation prior to click Huisgen is significantly more successful. Thus the reactions investigated here can be considered to be key elements of the chemical toolbox for the synthesis of highly sophisticated bioconjugates. [ABSTRACT FROM AUTHOR]

Hydrogen atom abstraction from the C5'-position of nucleotides in DNA results in direct strand scission by generating alkali-labile fragments from the oxidized nucleotide. The major damage consists in a terminus containing a 5'-aldehyde as part of an otherwise undamaged nucleotide. Moreover it is considered as a polymorphic DNA strand break lesion since it can be borne by any of the four nucleosides encountered in DNA. Here we propose an expeditious synthesis of oligonucleotides (ON) ending with this 5'-aldehyde group (5'-AODN). This straightforward and cheap strategy relies on Pfitzner--Moffatt oxidation performed on solid support followed by a transient protection of the resulting aldehyde function. This method is irrespective of the 5'-terminal nucleobase and most interestingly can be directly extended to RNA to produce the corresponding 5'-AORN. We also report preliminary results on recognition of 5'-AODN by base excision repair (BER) enzymes. [ABSTRACT FROM AUTHOR]

Under irradiation, Ru-TAP (TAP = 1,4,5,8-tetraazaphenanthrene) complexes tethered to oligonucleotides (Ru-ODN) hybridized to their complementary target sequences produce irreversible adducts with guanine (G) bases. The interesting feature is that the G bases that react in the double strand (DS) topology belong exclusively to the complementary strand; thus, no G base of the Ru-ODN strand participates in the production of these adducts. This highly specific photoreaction in the DS topology is demonstrated by gel electrophoresis analyses of different duplex sequences in which the positions of the G bases are varied. Atomistic molecular modelling simulations indicate that this specificity is due to important steric constraints for the intrastrand adduct formation in the duplex. Luminescence lifetime measurements furnish more detailed information on these different duplex systems. [ABSTRACT FROM AUTHOR]

An efficient method for the thioglycoconjugation of iodinated oligonucleotides by Buchwald-Hartwig-Migita cross-coupling under mild conditions is reported. The method enables divergent synthesis of many different functionalized thioglycosylated ODNs in good yields, without affecting the integrity of the other A, C, and G nucleobases., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Because the influence of the chemical structure of monomethine cyanine-oligo-2'-deoxyribonucleotide (ODN) conjugates on their binding and fluorescence properties has remained largely undetermined, we synthesized and studied a wide range of conjugates with various structural patterns. Different cyanine dyes such as thiocyanine, quinocyanine, and thiazole orange isomers were obtained. In the case of unsymmetrical cyanines, the linker was attached to either the quinoline or the benzothiazole nucleus. The influence of the ODN counterpart was evaluated by linking the cyanines to the 5'-end or to an internucleotidic phosphate. In the first case, the influence of neighboring nucleic bases was studied, whereas in the second, the stereochemical configuration at the phosphorus atom bearing the cyanine was investigated. We report here on relationships between the structures of the dyes and conjugates and some of their properties, such as the stability and fluorescence changes observed on their hybridization with the target sequence. This study provides useful information towards the design of ODN-cyanine conjugates.