Self-assembly of borononucleic acids : from ligation to polymerization

Mimer les processus biologiques par des méthodes s'affranchissant de la nécessité d'activation enzymatique est un défi pour la communauté des chimistes. Parmi ces processus nous nous sommes intéressés à la ligation et la polymérisation d'acides nucléiques. Les procédés chimiques existants nécessitent généralement l'emploi d'un activateur et conduisent en majorité à des jonctions internucléosidiques irréversibles, incompatibles avec les systèmes vivants. Pour réaliser la ligation et la polymérisation réversibles d'ADN en l'absence d'activation chimique ou enzymatique, nous avons utilisé des oligonucléotides modifiés par une fonction acide boronique qui a la propriété de se lier de manière covalente et réversible avec des fonctions cis 1,2 diol.Un analogue de la thymidine fonctionnalisé par un acide boronique a ainsi été synthétisé et incorporé à l'extrémité 5' d'un oligonucléotide. En présence d'une matrice et d'un partenaire 3' diol, une jonction boronate peut alors être obtenue. L'influence de la nature des fonctions à l'extrémité 3' du partenaire a été étudiée afin de déterminer les paramètres gouvernant la ligation et a notamment conduit à la formation d'une jonction oxazaborolidine en présence d'un partenaire aminoalcool. Par ailleurs, cette méthodologie a été appliquée à des processus visant à mimer la polymérisation par la formation de multiples jonctions boronates entre des oligonucléotides bifonctionnalisés par un acide boronique et un diol. Enfin l'auto polymérisation d'un duplexe en l'absence de matrice a été évaluée.Mimicry of biological processes by non enzymatic ways is a challenge for chemists. Among those processes, we have been focusing on the ligation and polymerization of nucleic acids. Reported chemical methods usually require an activator and lead mostly to irreversible internucleosidic linkage which are incompatible with living systems. To perform DNA ligation and polymerization under enzyme free and activator free conditions, we used modified oligonucleotides bearing a boronic acid function able to bind covalently and reversibly cis 1,2 diols.Thus, a thymidine analog functionalized by a boronic acid was synthesized and introduced at the 5' end of an oligonucleotide. In the presence of a template and a 3 end diol partner, a boronate junction can be obtained. Influence of the nature of functions at the 3' end of the partner have been studied to indentify the parameters governing the ligation and allowed the formation of an internucleosidic oxazaborolidine linkage with an aminoalcohol partner. In addition, this methodology has been applied to polymerization mimicking processes by the formation of multiple boronate junctions between bifunctionnal oligonucleotides bearing a boronic acid and a diol. Finally we evaluated the auto polymerization of a duplex in the absence of template

pH-controlled DNA- and RNA-templated assembly of short oligomers.

International audienceIn the area of artificial genetics the development of non-enzymatic self-organization of synthetic building blocks is critical for both providing biopolymers with extended functions and understanding prebiotic processes. While reversibility is believed to have played a major role in early functional genetic materials, we previously reported an efficient DNA-templated ligation of suitably designed 5′-end boronic acid and 3′-end ribonucleosidic half-sequences. Here, we report the enzyme-free and activation-free DNA- and RNA-templated assembly of bifunctional hexamers. The reversible assembly was found to be regio- and sequence specific and the stabilities of the resulting duplexes were compared to their nicked counterparts. To go further with our understanding of this unprecedented process we also examined an auto-templated duplex self-assembly representing a key step toward the evolution of sequence-defined synthetic polymers

Synthesis of 3′-deoxy-3′-iminodiacetic acid and 3′-deoxy-3′-aminodiethanol thymidine analogues and NMR study of their complexation with boronic acids

International audienceThe iminodiacetic acid and aminodiethanol moieties are known for their ability to generate with boronic acids bicyclic structures having a strong intramolecular N-B coordination. We describe here the convergent synthesis of 3'-deoxy-3'-iminodiacetic acid and 3'-deoxy-3'-aminodiethanol thymidine analogues. The abilities of these compounds to form boronate complexes with aliphatic or aromatic boronic acids were established by 1D and 2D H-1 and C-13 NMR. Moreover, conformational analysis of the newly synthesized compounds revealed a marked preference for an N-type sugar puckering