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Conception, synthèse, et évaluation de l'affinité de glyco-oligonucléotides et glycoclusters contre les lectines I et II de Pseudomonas aeruginosa

Abstract : Pseudomonas aeruginosa (PA) is a bacteria with a strong resistance to antibiotics.It’s an opportunistic germ involved in nosocomial infections and the infection of immunocompromised patients. Lectins are glycoproteins that bind saccharides reversibly with a low affinity. They are involved in bacteria protection mechanisms and virulence. In order to increase the affinity of saccharides to PA lectins I and II, we used multivalence and synthesized molecular decoys. Our strategy involves the synthesis of glycoclusters conjugated with a DNA tag in order to easily screen them on DNA arrays. We described here the design, the synthesis and the assembly of different building blocks allowing the synthesis of glyco-oligonucleotides,based on "Click" chemistry (CuAAc) and oligonucleotide chemistry. The screening of theglyco-oligonucleotides was completed by studies of molecular modelisation and by STD NMR.The best compounds from the screening were synthesized without the DNA tag in order to evaluate their abilities of inhibiting the biofilm formation of PA.
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Anthony Angeli. Conception, synthèse, et évaluation de l'affinité de glyco-oligonucléotides et glycoclusters contre les lectines I et II de Pseudomonas aeruginosa. Ingénierie biomédicale. Université Montpellier, 2016. Français. ⟨NNT : 2016MONTT194⟩. ⟨tel-01756847⟩

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