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Article Dans Une Revue Molecules Année : 2020

Synthesis of triazole-linked SAM-adenosine 2 conjugates: functionalization of adenosine at N-1 or N-6 position without protecting groups

Résumé

More than 150 RNA chemical modifications have been identified to date. Among them, methylation of adenosine at the N-6 position (m 6 A) is crucial for RNA metabolism, stability and other important biological events. In particular, this is the most abundant mark found in mRNA in mammal cells. The presence of a methyl group at the N-1 position of adenosine (m 1 A) is mostly found in ncRNA and mRNA and is mainly responsible for stability and translation fidelity. These modifications are installed by m 6 A and m 1 A RNA methyltransferases (RNA MTases), respectively. In human, deregulation of m 6 A RNA MTases activity is associated with many diseases including cancer. To date, the molecular mechanism involved in the methyl transfer, in particular substrate recognition, remains unclear. We report the synthesis of new SAM-adenosine conjugates containing a triazole linker branched at the N-1 or N-6 position of adenosine. Our methodology does not require protecting groups for the functionalization of adenosine at these two positions. The molecules described here were designed as potential bisubstrate analogues for m 6 A and m 1 A RNA MTases that could be further employed for structural studies. This is the first report of compounds mimicking the transition state of the methylation reaction catalyzed by m 1 A RNA MTases.
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Dates et versions

hal-02915430 , version 1 (14-08-2020)

Identifiants

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Colette Atdjian, Dylan Coelho, Laura Iannazzo, Mélanie Etheve-Quelquejeu, Emmanuelle Braud. Synthesis of triazole-linked SAM-adenosine 2 conjugates: functionalization of adenosine at N-1 or N-6 position without protecting groups. Molecules, 2020, 25 (14), pp.3241. ⟨10.3390/molecules25143241⟩. ⟨hal-02915430⟩
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