Acyclic Phosphonate Nucleotides and Human Adenylate Kinases: Impact of a Borano Group on alpha-P Pos
Acyclic Phosphonate Nucleotides and Human Adenylate Kinases: Impact of a Borano Group on alpha-P Position.
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.
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.
Laboratoire d\’Enzymologie, Université Paris, Paris, France.