Chapter 7
An Introduction to Medicinal Chemistry · 3 exercises
Problem 1
It is known that the amino acid at position 523 of the cyclooxygenase enzyme is part of the active site. In the isoenzyme COX-1, this amino acid is isoleucine, whereas in COX-2, it is valine. Suggest how such information could be used in the design of drugs that selectively inhibit COX-2.
4 step solution
Problem 4
Why should a transition state be bound more strongly to an enzyme than a substrate or a product?
4 step solution
Problem 8
Cytidine deaminase is an enzyme that converts cytidine to uridine. Suggest a mechanism by which this reaction might occur, considering that a highly conserved water molecule is present in the active site. Zebularine is a natural product that is converted into a highly potent transition-state (TS) inhibitor of the enzyme \(\left(K_{1}=1.2 \mathrm{pM}\right)\) when it is in the active site. Suggest what the structure of the TSinhibitor might be and why it is so effective. Explain why 3,4 -dihydrozebularine has a binding affinity that is only \(30 \mu \mathrm{M} .\)
5 step solution