Gas-phase experimental and computational studies of human hypoxanthine-guanine phosphoribosyltransferase substrates: Intrinsic properties and biological implications

The gas-phase acidity and proton affinity of nucleobases that are substrates for the enzyme human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) have been examined using both theoretical and experimental methods. These thermochemical values have not heretofore been measured and provide experimental data to benchmark the computational results. HGPRT is important for human health and is also a key target for antiparasitic chemotherapy. We use our gas-phase results to lend insight into the HGPRT mechanism and also propose kinetic isotope studies that could potentially differentiate between possible mechanisms.