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

Index: Nucleosides Nucleotides Nucleic Acids 27(4) , 319-31, (2008)

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Abstract

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.

Related Compounds

  • pinacolyl methylph...

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