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Yoann Colas

Constrained oligonucleotides based chiral catalyst

Published on 13 July 2022
Thesis presented July 13, 2022

Since the industrial revolution, chemistry has continued to flourish and develop new and increasingly efficient processes to meet the needs of a growing society. However, given the current climatic conditions, it has become essential to develop a greener and more eco-responsible chemistry. In order to meet the requirements of this "green chemistry", the field of artificial metalloenzymes, combining both bio-inspired and catalytic approaches, has been particularly explored.
Due to their high folding polymorphism, depending on the nature of the sequence as well as the salt environment, G-quadruplexes are versatile DNA-based catalytic entities for selective asymmetric reactions. However, it has been shown that the enantioselectivity of catalytic reactions is highly dependent on the topology predominantly adopted by the G-quadruplex. Indeed, it is possible to observe different enantioselectivities depending on the nature of the predominant topology adopted. In this context, our laboratory has developed the concept of RAFT (for "Regioselectively Addressable Functionalized Template") to assemble stable G-quadruplex mimes.
The first part of our study consisted in synthesizing a panel of constrained G-quadruplex, using a functional cyclopeptide platform and distinct chemoselective ligations. Then, in a second step, the synthesized structures were analyzed by circular dichroism in order to confirm the predominantly adopted topologies and the enhanced stability compared to the unconstrained structures. Finally, catalytic reactions for the sulfoxidation of thioether derivatives were performed to determine the impact of each topology on the enantioselectivity of this reaction.

Asymmetric catalysis, G-quadruplex, oligonucleotides, Sulfoxidation