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Publication : Nucleosides, nucleotides & nucleic acids

Acyclic phosphonate nucleotides and human adenylate kinases: impact of a borano group on alpha-P position

Team: Group: Biochemistry and chemobiology
Team: Archived: Group : Chemistry and Biocatalysis
Team: Chemistry of Biomolecules
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nucleosides, nucleotides & nucleic acids - 01 Apr 2008

Topalis D, Alvarez K, Barral K, Munier-Lehmann H, Schneider B, Véron M, Guerreiro C, Mulard L, El-Amri C, Canard B, Deville-Bonne D

Link to Pubmed [PMID] – 18404568

Nucleosides Nucleotides Nucleic Acids 2008 Apr;27(4):319-31

Adenylate kinases are involved in the activation of antiviral drugs such as the acyclic phosphonates analogs PMEA and (R)PMPA. We examine the in vitro phosphorylation of PMEA and PMPA bearing a borano- or a H- group on the phosphorus atom. The alpha-borano or alpha-H on PMEA and PMPA were detrimental to the activity of recombinant human AMP kinases 1 and 2. Docking PMEA to the active site of AMP kinase 1 indicated that the borano group may prevent two conserved critical Arg interactions with the alpha-phosphate, resulting in substrate bad positioning.