Enzymes As Drug Targets l11 Flashcards
(23 cards)
What is the primary function of enzymes in the body?
Enzymes act as catalysts that speed up chemical reactions without being consumed in the process.
What is the role of the active site in enzyme function?
The active site is the specific area on the enzyme where substrates bind and react.
What type of interactions are involved in substrate binding to the active site?
- Ionic bonds
- Hydrogen bonding
- Dipole-dipole interactions
- Ion-dipole interactions
- Dispersion/hydrophobic interactions
What must binding interactions between substrates and enzymes achieve?
They must be strong enough to hold the substrate long enough for the reaction to occur, yet weak enough to allow the product to depart.
What is the purpose of enzyme inhibitors in medicinal chemistry?
To design molecules that block the active site of enzymes, preventing substrate binding and inhibiting enzyme activity.
What are the six major classes of enzymes?
- Oxidoreductases
- Transferases
- Hydrolases
- Lyases
- Isomerases
- Ligases/synthetases
What characterizes irreversible inhibition?
The inhibitor binds irreversibly to the active site, forming a covalent bond, blocking substrate access.
True or False: Increasing substrate concentration can reverse irreversible inhibition.
False
Give an example of an irreversible inhibitor.
- Aspirin
- Clavulanic acid
What defines competitive reversible inhibitors?
They bind reversibly to the active site, blocking substrate access, and their inhibition can be reversed by increasing substrate concentration.
What is the significance of the Ki value in competitive inhibition?
The smaller the Ki, the stronger the inhibition.
What do HIV protease inhibitors do?
They mimic the substrate, preventing the cleavage of large protein structures into active forms.
What is uncompetitive inhibition?
Inhibitors that bind only to the enzyme-substrate complex, preventing the transformation of the substrate.
What is the effect of mixed inhibition?
Inhibitors bind to both the free enzyme and the enzyme-substrate complex, and increasing substrate concentration does not affect inhibition.
What are allosteric inhibitors?
Inhibitors that bind at allosteric sites, causing a change in the enzyme’s shape that makes the active site unrecognizable to the substrate.
How do enzyme inhibitors achieve selective toxicity against microorganisms?
By targeting enzymes that are unique to microorganisms, such as penicillin targeting bacterial enzymes.
What are the two reactions catalyzed by HIV-1 integrase?
- Removal of terminal GT dinucleotide at the 3’-ends of viral DNA
- Insertion of viral DNA into host DNA
What characterizes protein kinases as drug targets?
They catalyze the transfer of phosphate groups from ATP to specific amino acids in target proteins.
What are the classes of protein kinase inhibitors?
- Type I: Bind to active site in active form
- Type II: Bind to active site in inactive form
- Type III: Allosteric inhibitors binding to inactive enzyme
- Type IV: Bind to distant sites
- Type V: Bivalent inhibitors
- Type VI: Covalent bond formers
What is one reason for toxicity issues with enzyme inhibitors?
Off-target effects where the inhibitor affects unintended enzymes or proteins, disrupting normal biological processes.
What strategies can enhance selectivity in enzyme inhibition?
- Exploiting unique structural features
- Allosteric inhibition
- Substrate mimicry
- Computational modeling
- Optimizing pharmacokinetics
What is the importance of understanding the structure and mechanism of the target enzyme in drug design?
It helps identify unique features that can be exploited for specificity in inhibitor design.
Fill in the blank: Inhibitors designed to bind to allosteric sites can lead to greater _______.
[selectivity]
