Medicinal Chemistry Chapter 07 Key

Type: multiple choice Title: Chapter 07 - Question 01 01) Which of the following descriptions best describes a competitive enzyme inhibitor? Feedback: A competitive or reversible inhibitor is in equilibrium between the enzymebound state and the unbound state. Therefore, increasing the substrate concentration will allow the substrate to compete for active site occupancy. This will result in a decrease in inhibition. The agent that binds to an active site and undergoes a reaction is called a substrate. An agent that binds to an active site and inhibits the enzyme, but which is not displaced by increasing the concentration of substrate is an irreversible inhibitor. An agent that binds to a different binding site from the active site and affects the activity of the enzyme is an allosteric inhibitor. incorrect a.# A drug that binds to an active site and undergoes a reaction. Correct b.# incorrect c.# incorrect d.# A drug that binds to an active site and inhibits the enzyme, but which is displaced by increasing the concentration of substrate. A drug that binds to an active site and inhibits the enzyme, but which is not displaced by increasing the concentration of substrate. A drug that binds to a different binding site from the active site and affects the activity of the enzyme. END OF QUESTION Type: multiple choice Title: Chapter 07 - Question 02 02) Which of the following descriptions best describes an allosteric inhibitor? Feedback: An agent that binds to a different binding site from the active site and affects the activity of the enzyme is an allosteric inhibitor. An agent that binds to an active site and inhibits the enzyme, but which is displaced by increasing the concentration of substrate is called a competitive or reversible inhibitor. The agent that binds to an active site and undergoes a reaction is called a substrate. An agent that binds to an active site and inhibits the enzyme, but which is not displaced by increasing the concentration of substrate is an irreversible inhibitor. incorrect a.# A drug that binds to an active site and undergoes a reaction. incorrect b.# incorrect c.# Correct d.# A drug that binds to an active site and inhibits the enzyme, but which is displaced by increasing the concentration of substrate. A drug that binds to an active site and inhibits the enzyme, but which is not displaced by increasing the concentration of substrate. A drug that binds to a different binding site from the active site and affects the activity of the enzyme. END OF QUESTION Type: multiple choice Title: Chapter 07 - Question 03 03) Which of the following is not true of suicide substrates? Feedback: Suicide substrates form covalent bonds with the active site of the target enzyme and so act as irreversible inhibitors. When the enzyme binds the drug, the catalytic mechanism activates the suicide substrate and a strong covalent bond is formed between the drug and the active site. The drug is now permanently linked to the active site and causes irreversible inhibition. The enzyme ultimately commits suicide by binding to the suicide substrate. incorrect a.# They are activated by the enzyme-catalysed reaction mechanism. Correct b.# They react reversibly with the enzyme. incorrect c.# They form a covalent bond with the active site once activated. incorrect d.# They are so called because they cause the target enzyme to commit suicide by reacting with them. END OF QUESTION Type: multiple choice Title: Chapter 07 - Question 04 04) Which statement best describes the relevance of an allosteric binding site to medicinal chemistry? Feedback: Designing drugs to interact with allosteric binding site allows a method of regulating enzyme activity, other than using inhibitors which bind to the active site. Allosteric binding sites cannot be said to be more or less hydrophobic than active sites. Each binding site is different in that respect, regardless of whether it is an active site or an allosteric binding site. There is also no reason to suppose that allosteric binding sites should be capable of binding a wider variety of drug structures than an active site. The answer ‘drugs can be designed based on the transition state of the enzyme-catalysed reaction‘ is wrong since this refers to drugs which bind to the active site and not the allosteric binding site. incorrect a.# It is more hydrophobic than normal binding sites and accepts hydrophobic drugs in preference to hydrophilic drugs. incorrect b.# A larger variety of drug structures will bind to the allosteric site than to the active site. Correct c.# Drugs can be designed based on the structure of the endogenous chemicals which bind to allosteric sites and control enzyme activity. incorrect d.# Drugs can be designed based on the transition state of the enzyme-catalysed reaction. END OF QUESTION Type: multiple choice Title: Chapter 07 - Question 05 05) Identify the kind of bonding forces which are typically involved in binding a drug to an enzyme’s active site. Feedback: The active sites of different enzymes vary in the relative number of ionic interactions, hydrogen bonds, and van der Waals interactions that are used to bind a drug. incorrect a.# Predominantly van der Waals interactions. incorrect b.# Predominantly ionic bonds. incorrect c.# Predominantly hydrogen bonds. Correct d.# A combination of different intermolecular binding interactions. END OF QUESTION Type: matching Title: Chapter 07 - Question 06 06) Identify an amino acid in an active site whose residue could bind a drug, principally by: Feedback: Serine has a hydroxyl group which can take part in hydrogen bonding. Aspartic acid has a residue containing a carboxylic acid group that can take part in ionic interactions if it is ionised. Valine has an alkyl side chain that can interact by van der Waals interactions. Glycine has no residue available for bonding interactions. a.# Hydrogen bonding = Serine b.# Ionic bonding = Aspartic acid c.# Van der Waals interactions = Valine d.# None of the above = Glycine END OF QUESTION Type: multiple choice Title: Chapter 07 - Question 07 07) Which of the following descriptions is most accurate regarding binding sites and binding regions? Feedback: A binding region is part of the binding site and is capable of forming a specific binding interaction with a drug. The binding region may contain a particular functional group that can participate in a hydrogen bond or an ionic bond. Alternatively, it may be hydrophobic in nature and interact by van der Waals interactions. incorrect a.# A binding site is part of a binding region. Correct b.# A binding region is part of a binding site. incorrect c.# A binding region is the same as a binding site. incorrect d.# A binding region is part of a drug whereas a binding site is part of a macromolecular target. END OF QUESTION Type: multiple choice Title: Chapter 07 - Question 08 08) What type of plots can be used to determine whether an enzyme inhibitor is competitive or non-competitive? Feedback: Michaelis-Menten plots are used to study how the enzyme-catalysed rate of reaction is affected by substrate concentration. Schild plots are used to study the effect of antagonists on receptors. Displacement curves are used to measure IC50 values for receptor antagonists. Lineweaver-Burk plots are used to determine whether an enzyme inhibitor is competitive or non competitive. incorrect a.# Michaelis-Menten plots. incorrect b.# Schild plots. incorrect c.# Displacement plots. Correct d.# Lineweaver-Burk plots. END OF QUESTION