Etude par RMN et modélisation moléculaire des structures de la séquence ARN initiant la dimérisation chez VIH-1Lai et de son analogue ADN

Abstract : Like all retroviruses, the human immunodeficience virus (HIV) genome is made up of two identical copies of genomic RNA. Those are related in a non-covalent way to their 5' leader. This dimerization phenomenon interferes with various key stages of the retroviral cycle life. Therefore, the dimerization inhibition represents a new way of processing against HIV. The first part of this work concerns the RNA SL1 sequence who initiating the HIV-1Lai dimerization. We were interested in the structural determination, by NMR and molecular modeling, of the species present in the dimerization process. After having isolated both RNA different dimer, we highlighted the stable dimer structure which makes it possible to advance assumptions of their relative stability. The second part of this work still concerns the study of the deoxyribose SL1 fragment. Here again, two forms of different stability may be isolate. The unstable dimer is organized in the form of "kissing-complex" and represents the first structure of this type elucidated for a DNA. The structure of stable dimer remains of type "kissing-complex" although presenting distinctions at the origin of the stability difference. The presence of the hydroxyl group distinguishing DNA from RNA explains this behavior difference. These structural investigations constitute a solid base study in the "drug-design" strategies implying the development of inhibitors likely to interfere with the dimerization phenomenon.
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Florent Barbault. Etude par RMN et modélisation moléculaire des structures de la séquence ARN initiant la dimérisation chez VIH-1Lai et de son analogue ADN. Autre. Université d'Orléans, 2001. Français. ⟨tel-00009954⟩

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