Nucleosides, Nucleotides & Nucleic Acids 2008-04-01

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

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

文献索引：Nucleosides Nucleotides Nucleic Acids 27(4) , 319-31, (2008)

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摘要

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.