Gas Phase Studies of Purine Base Analogs: Intrinsic Properties and Hypoxanthine-Guanine-(Xanthine) Phosphoribosyltransferase (HG(X)PRT)

Abstract The gas-phase acidity and proton affinity of purine nucleobases that are found to be inactive 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 an antimalarial target; our gas-phase results lend insight into the Pf HG(X)PRT mechanism, providing a potential means of predicting enzyme substrate activity.