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

The gas-phase acidity and proton affinity of nucleobases that are substrates for the enzyme Plasmodium falciparum hypoxanthine-guanine-(xanthine) phosphoribosyltransferase ( Pf HG(X)PRT) have been examined using both computational and experimental methods. These thermochemical values have not heretofore been measured and provide experimental data to benchmark the theoretical results. Pf HG(X)PRT is a target of interest in the development of antimalarials. We use our gas-phase results to lend insight into the Pf HG(X)PRT mechanism, and also propose kinetic isotope studies that could potentially differentiate between possible mechanisms.