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PDA Exam 2, Part 6
Molecular Mechanisms- drug targets
20
Pharmacology
Professional
03/07/2012

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Cards

Term
Describe B-DNA
Definition
Right handed
10bp per twist
Term
Describe Z-DNA
Definition
Left handed
Less stable, exposes hydrophobic inner core
Found in viruses
Term
Describe the mechanism of action of actionomycin D
Definition
It intercalates into DNA, interfering with the structure
Term
Do intercalators form covalent bonds? Do alkylating agents?
Definition
Intercalators do not form covalent bonds

Alkylating agents do
Term
What is the mechanism of action of mechlorethamine hydrochloride (mustard gas)?
Definition
Its chlorine arms alkylate the N-9 position of guanine

Since it has 2 arms, it can crosslink, preventing DNA unwinding for replication
Term
List three drugs that target nucleic acid biosynthesis
Definition
Sulfonamides, trimethoprim, pyrimethamine
Term
Describe the mechanism of action of trimethoprim
Definition
Trimethoprim prevents the use of folate (can work alongside sulfonamides) by specifically targeting DHFR

Most bacteria cannot transport exogenous folates
Term
Define pyrimethamine
Definition
Inhibitor of DHFR, specific for plasmodium species
Term
What is the mechanism of action of flucytosine?
Definition
It is an antifungal agent, only fungi have cytosine deaminase that converts flucytosine to 5-FU
Term
Define gyrase/topoisomerase
Definition
Enzymes that introduces negative supercoils into DNA, allowing for unwinding (decatenation)
Term
What antibiotic class inhibit gyrase?
Definition
Fluoroquinolones
Term
How is acyclovir a good anti-cancer agent?
Definition
It's 3' hydroxyl is recognized for chain elongation but it significantly slows down the enzyme
Term
Describe the basic structure of a quinolone
Definition
Two ring structures with 1 nitrogen in each

Fluoroquinolones include a fluorine
Term
Describe the mechanism of action of AZT
Definition
Reverse transcriptase inhibitor- the N3 inhibits the enzyme
Term
Describe the mechanism of action of pentostatin
Definition
transition state analog of ADA (aminosine deaminase)
Term
Describe the mechanism of action of allopurinol
Definition
Xanthine oxidase inhibitor

Inhibits HPRT by acting as a xanthine analog
Term
What is the difference between primary and secondary gout?
Definition
Primary is when people get it genetically

Secondary is when cancer patients develop gout because of the large number of cells breaking down
Term
Describe the mechanism of action of chloramphenicol

How do bacteria become resistant to it?
Definition
Stops protein synthesis by inhibiting 50S ribosomal subunit

D-form only

Resistant bacteria get plasmids with a new enzyme, CAT, which acetylates and inactivates chloramphenicol
Term
Describe the mechanism of action of aminoglycosides
Definition
Binds to 30S subunit of bacterial ribosomes

Resistant bacteria adenylate and phosphorylate them

Synergistic with penicillin
Term
List four aminoglycosides
Definition
Kenamycin, gentamicin, amikacin, tobramycin
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