Acyclic Phosphonate Nucleotides and Human Adenylate Kinases: Impact of a Borano Group on α-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 α-borano or α-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 α-phosphate, resulting in substrate bad positioning. [ABSTRACT FROM AUTHOR]