Lecture 3: Drugs as Enzyme Inhibitors Flashcards
How do small-molecule drugs inhibit the catalytic activity of enzymes and therefore have therapeutic value?
Small molecule drugs mimic the natural ligands of an enzyme. They bind by mimicking the natural substrate, bind in front of the active site to prevent substrate entry or bind away from the catalytic site and cause conformation changes in the enzyme, changing it’s activity.
What chemical properties of drugs and design strategies are used to give therapeutic efficacy and safety?
High affinity, critical for drug activity, is achieved by rationale design with structural knowledge from complexes with natural ligands and predicted transition-states, and using basic concepts of molecular recognition, i.e. active-site complementarity.
What does the structure of the enzyme-drug complex allow us to do?
It enables us to understand drug activity and leads to improving drug properties.
What is a reversible inhibitor and examples?
Reversible inhibition inactivates an enzyme through non covalent, more easily reversed interactions. Include competitive inhibitors and noncompetitive inhibitors. Examples include TS-analogues, active site inhibitors and derivatives of natural ligand analogues.
What is an irreversible inhibitor and examples?
Irreversible inhibition inactivates an enzyme by covalently bonding to a particular group at the active site. The binding positions a chemically reactive group near side-chains to form a covalent bond between drug and enzyme. One examples is a mechanism-based irreversible inhibitor that reacts with active site residues similar of that to the natural substrate.
