Effect of the phosphate substrate on drug-inhibitor binding to human purine nucleoside phosphorylase.

The thermodynamics of the drug-inhibitors acyclovir, ganciclovir, and 9-benzylguanine binding to human purine nucleoside phosphorylase (hsPNP) were determined from isothermal titration calorimetry as a function of the substrate phosphate ion (Pi) concentration from 0 to 0.125 M and temperature from 15 degrees C to 35 degrees C. At 25 degrees C and with an increase in the Pi concentration from 0 to 50mM, acyclovir binding becomes more entropically-driven and ganciclovir binding becomes more enthalpically-driven.

Effect of the distal C162S mutation on the energetics of drug binding to p38alpha MAP kinase.

The binding reactions of the inhibitor drugs, SB 203580, SKF 86002, and p38 INH.1 to the isoforms 1 and 2 splice variants of p38alpha MAP kinase and their C162S mutants, as determined from ITC measurements from 25 to 35 degrees C, are totally enthalpically driven with binding constants ranging from 10(7)M(-1) for SKF 86002 and SB 203580 to 10(9)M(-1) for p38 INH.1.