Gas-Phase Studies of Hypoxanthine-Guanine-(Xanthine) Phosphoribosyltransferase (HG(X)PRT) Substrates

The gas-phase acidity and protonaffinity of nucleobasesthat aresubstrates for the enzyme Plasmodium falciparum hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (Pf HG-(X)-PRT) have been examined using both computationaland experimental methods. These thermochemical values have not heretoforebeen measured and provide experimental data to benchmark the theoreticalresults. Pf HG-(X)-PRT is a target of interest in thedevelopment of antimalarials. We use our gas-phase results to lendinsight into the Pf HG-(X)-PRT mechanism, and alsopropose kinetic isotope studies that could potentially differentiatebetween possible mechanisms.

Automated summary

In this study, the gas-phase acidity and proton affinity of nucleobases that act as substrates for Pf HG-(X)-PRT were investigated using computational and experimental methods. These previously unmeasured thermodynamic values provide experimental data to validate theoretical results. The findings can offer insights into the mechanism of Pf HG-(X)-PRT and suggest possible kinetic isotope studies to distinguish between mechanisms.