Binding mechanisms thermodynamic effects

In this chapter we described the thermodynamics of enzyme-inhibitor interactions and defined three potential modes of reversible binding of inhibitors to enzyme molecules. Competitive inhibitors bind to the free enzyme form in direct competition with substrate molecules. Noncompetitive inhibitors bind to both the free enzyme and to the ES complex or subsequent enzyme forms that are populated during catalysis. Uncompetitive inhibitors bind exclusively to the ES complex or to subsequent enzyme forms. We saw that one can distinguish among these inhibition modes by their effects on the apparent values of the steady state kinetic parameters Umax, Km, and VmdX/KM. We further saw that for bisubstrate reactions, the inhibition modality depends on the reaction mechanism used by the enzyme. Finally, we described how one may use the dissociation constant for inhibition (Kh o.K or both) to best evaluate the relative affinity of different inhibitors for ones target enzyme, and thus drive compound optimization through medicinal chemistry efforts. 

The purpose of this chapter is to explore the properties and reactions of various Pt-nucleobase complexes. After a short description of various binding modes, attention will be paid on the effects of coordinated platinum. Topics include, e.g., isomerization, thermodynamic stability, and solvolyt-ic reactions of Pt-nucleobase complexes. Finally, factors affecting the mechanism and kinetics of substitution reactions by various nucleophiles will be discussed. 

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