Final Flashcards
By what mechanism do DNA polymerase inhibitors such as aciclovir work?
DNA polymerization requires a hydroxyl which acyclovir lacks, thus polymerization is halted after the addition of aciclovir triphosphate.
What makes aciclovir more specific to viral-infected cells?
The first phosphate is added by viral thymidine kinase, which aciclovir has much greater selectivity for.
What are the main targets in the HIV life cycle
fusion/entry; reverse transcriptase; HIV protease; integrase
How do nucleoside RT inhibitors work?
Chain termination at the step of building DNA onto the RNA template
What is the major difference in the mechanism for non-nucleoside RT inhibitors vs. NRTIs
NNRTIs bind allosterically to reverse transcriptase to change conformation to inactive
Explain fxn of HIV protease
Cleaves polyproteins into fxnl mature proteins
What design principle were important in the first HIV protease inhibitors
Transition state isotere of the peptide bond btwn phenylalanine and proline; the binding sites of the other residues in the viral polypeptide POL
Why do symmetric protease inhibitors show selectivity to viral proteases
Mammalian proteases are not symmetric
How do entry/fusion inhibitors work
Can bind to gp120 or gp41; block CD4 or CCR5
How do integrase inhibitors work?
Bind Mg 2+ ions in the active site to block the binding of DNA
What is neuraminidase and how is it important to the influenza life cycle?
Cleaves sialic acid to degrade mucus layer and allow virus to reach surface epithelial cells
What design principles are important for NA inhibitors?
The transition state of the carboxylate ion being in the equatorial position interacting arginine residues
How do sulfonamides work against bacteria?
Inhibits the production of tetrahydrofolate, which ultimately inhibits purine synthesis (inhibits dihydropteroate synthetase)
What enzyme does penicillin inhibit and what is the general mechanism?
Transpeptidase, responsible for crosslinking bacterial cell wall; serine residue hydrolyzes the lactam ring which binds penicillin to active site and blocks bacterial peptide and water from entering active site
What is the significance of the double ring system in penicillin?
The bond angles are restricted, thus there is no resonance between the nitrogen and carbonyl, making the amide bond sensitive to hydrolysis/cleavage