BPS 2110 FINAL EXAM QUESTIONS
AND ANSWERS
What are the 4 key requirements for modern drug safety testing in animals? Why is
each of these requirements important? - Answer--Smallest and fewest animals possible.
-Two species, at least one primate (usually rats, drugs, monkeys).
-Blood sample to ensure the drug is bioavailable.
-Use of relevant dose.
Briefly describe how agencies such as the FDA and Health Canada operate. - Answer-
Companies do all the testing and provide their data to the FDA. The FDA checks the
data and ensures it matches the guidelines. The companies monitor their products and
the FDA provide inspections for manufacturing.
Why do you think it is important that the government does not perform safety testing? -
Answer-It is very expensive and taxpayers would pay for this.
Why do you think it is important that the drug industry does not pay user fees for
regulation? - Answer-The government should be wanting to receive this information to
ensure the safety of their population.
What are the 5 major classes of amino acids? Give an example of an amino acid in
each class. - Answer--Non-polar: Valine
-Polar: Serine
-Acidic: Aspartic acid
-Basic: Lysine
-Unique: Glycine
18 of the common amino acids have an S configuration at the a-carbon, however one
amino acid exists in the R configuration at this position. Which one and why? - Answer-
Cysteine. Sulfur has a higher atomic weight than nitrogen, which allows the R
configuration to be possible.
What is the primary structure of an amino acid? - Answer-A linear chain of amino acids.
What is the secondary structure of an amino acid? - Answer-An alpha-helix or beta-
pleaded sheet of amino acids.
,What is the tertiary structure of an amino acid? - Answer-The three-dimensional
structure of the protein.
What is the quaternary structure of an amino acid? - Answer-The three-dimensional
structure of multiple proteins.
What are the four types of secondary protein structure? - Answer--Alpha-helix
-Beta-pleated sheet
-Loop
-Turn
What is the structure of the alpha-helix and what causes it to form? - Answer-Cylinder-
type structure that displays its side chains to the outside. It forms from hydrogen bonds
between amide groups about 4 amino acids apart.
What is the structure of the beta-pleated sheet and what causes it to form? - Answer-
Flat, zig-zag shape sheet that points from the N to the C terminus, or from the C to the
N terminus. It holds itself together with other B-sheets. Several sheets may curl upon
themselves to form B-barrels.
What is the structure of the beta-turns and what causes them to form? - Answer-Areas
which change direction by almost 180° in 3 or 4 amino acids. These form due to
hydrogen bonding with nearby amide groups and are favoured by glycine or proline.
What is the structure of the loops and what causes them to form? - Answer-Areas of
otherwise undefined secondary structure.
Explain why the amide bonds in peptides usually only adopt either cis or trans
conformations. - Answer-Due to its double bond character. This means that the bond
(C-N) cannot rotate freely and only favours two positions.
Between the cis and trans conformation for the amide bonds in peptides, which
conformation is most common? - Answer-s-trans conformation. There is less steric
hinderance.
Why is proline the only amino acid that does not show a
preference for one amide conformation over the other? - Answer-It forms a closed ring
with the amide and the functional group. This gives similar sterics in both conformations.
What are the four types of non-bonding interactions responsible for maintaining tertiary
structure? - Answer--Hydrogen bonding
-Electrostatics
-Van der Waals interactions
-Dipole-dipole interactions
, What are the two enzymes of the AIDS virus that is used to replicate its genetic
information? - Answer--Reverse transcriptase
-RNAse H
What characteristics of the enzymes of the AIDS virus contribute to HIV's exceptionally
high mutation rate? - Answer--Reverse transcriptase is a sloppy enzyme that makes lots
of mistakes.
-RNAse H destroys the viral RNA template as the DNA strand is being made. Therefore,
no error correction (proofreading) is available.
What key aspect of anti-HIV drug structure has made possible therapies with
dramatically reduced side effects? - Answer-Certain pseudoeneatiomer nucleosides are
substrates for host kinases, and the resulting nucleotides are substrates for HIV reverse
transcriptase. This results in chain termination of the viral DNA. Host polymerases will
not accept pseudoenantiomer nucleotides as substrates, and so these drugs are unable
to chain terminate host nucleic acid synthesis.
What is the key structural element that gives rise to this "clean" profile? - Answer-A
pseudoenantiomer of a natural nucleoside.
What is a pseudoenantiomer? - Answer-A pseudoenantiomer is a stereoisomer that is
not a true enantiomer because it isn't an exact mirror image usually hindered by steric
conformation.
Why does this feature make 3-TC so selective? - Answer-The pseudoenantiomer is
accepted by HIV reverse transcriptase and becomes incorporated into viral nucleic acid.
The drug acts like a chain terminator and stops nucleic acid replication. Because it is a
pseudoenantiomer, it will not be accepted as a substrate by host polymerases. Because
it does not inhibit any host enzymes or nucleic acid production, it does not produce a lot
of side effects.
What is meant by the term retrovirus? - Answer-Virus carries its genetic information in
the form of RNA. The RNA is translated into double stranded DNA inside the cell.
What is the key enzyme found in retroviruses that give rise to this behavior? - Answer-
Reverse transcriptase.
What general drug strategy is used to inhibit this enzyme? - Answer-Rational drug
design using chain termination and non-natural sugar nucleoside analogues.
What is the reaction of the process used to biosynthetically link isoprene units together?
- Answer-An SN2 reaction followed by an E1 reaction.
What is the source of most of the cholesterol in humans? - Answer-Made in the liver
from saturated and trans fats.
AND ANSWERS
What are the 4 key requirements for modern drug safety testing in animals? Why is
each of these requirements important? - Answer--Smallest and fewest animals possible.
-Two species, at least one primate (usually rats, drugs, monkeys).
-Blood sample to ensure the drug is bioavailable.
-Use of relevant dose.
Briefly describe how agencies such as the FDA and Health Canada operate. - Answer-
Companies do all the testing and provide their data to the FDA. The FDA checks the
data and ensures it matches the guidelines. The companies monitor their products and
the FDA provide inspections for manufacturing.
Why do you think it is important that the government does not perform safety testing? -
Answer-It is very expensive and taxpayers would pay for this.
Why do you think it is important that the drug industry does not pay user fees for
regulation? - Answer-The government should be wanting to receive this information to
ensure the safety of their population.
What are the 5 major classes of amino acids? Give an example of an amino acid in
each class. - Answer--Non-polar: Valine
-Polar: Serine
-Acidic: Aspartic acid
-Basic: Lysine
-Unique: Glycine
18 of the common amino acids have an S configuration at the a-carbon, however one
amino acid exists in the R configuration at this position. Which one and why? - Answer-
Cysteine. Sulfur has a higher atomic weight than nitrogen, which allows the R
configuration to be possible.
What is the primary structure of an amino acid? - Answer-A linear chain of amino acids.
What is the secondary structure of an amino acid? - Answer-An alpha-helix or beta-
pleaded sheet of amino acids.
,What is the tertiary structure of an amino acid? - Answer-The three-dimensional
structure of the protein.
What is the quaternary structure of an amino acid? - Answer-The three-dimensional
structure of multiple proteins.
What are the four types of secondary protein structure? - Answer--Alpha-helix
-Beta-pleated sheet
-Loop
-Turn
What is the structure of the alpha-helix and what causes it to form? - Answer-Cylinder-
type structure that displays its side chains to the outside. It forms from hydrogen bonds
between amide groups about 4 amino acids apart.
What is the structure of the beta-pleated sheet and what causes it to form? - Answer-
Flat, zig-zag shape sheet that points from the N to the C terminus, or from the C to the
N terminus. It holds itself together with other B-sheets. Several sheets may curl upon
themselves to form B-barrels.
What is the structure of the beta-turns and what causes them to form? - Answer-Areas
which change direction by almost 180° in 3 or 4 amino acids. These form due to
hydrogen bonding with nearby amide groups and are favoured by glycine or proline.
What is the structure of the loops and what causes them to form? - Answer-Areas of
otherwise undefined secondary structure.
Explain why the amide bonds in peptides usually only adopt either cis or trans
conformations. - Answer-Due to its double bond character. This means that the bond
(C-N) cannot rotate freely and only favours two positions.
Between the cis and trans conformation for the amide bonds in peptides, which
conformation is most common? - Answer-s-trans conformation. There is less steric
hinderance.
Why is proline the only amino acid that does not show a
preference for one amide conformation over the other? - Answer-It forms a closed ring
with the amide and the functional group. This gives similar sterics in both conformations.
What are the four types of non-bonding interactions responsible for maintaining tertiary
structure? - Answer--Hydrogen bonding
-Electrostatics
-Van der Waals interactions
-Dipole-dipole interactions
, What are the two enzymes of the AIDS virus that is used to replicate its genetic
information? - Answer--Reverse transcriptase
-RNAse H
What characteristics of the enzymes of the AIDS virus contribute to HIV's exceptionally
high mutation rate? - Answer--Reverse transcriptase is a sloppy enzyme that makes lots
of mistakes.
-RNAse H destroys the viral RNA template as the DNA strand is being made. Therefore,
no error correction (proofreading) is available.
What key aspect of anti-HIV drug structure has made possible therapies with
dramatically reduced side effects? - Answer-Certain pseudoeneatiomer nucleosides are
substrates for host kinases, and the resulting nucleotides are substrates for HIV reverse
transcriptase. This results in chain termination of the viral DNA. Host polymerases will
not accept pseudoenantiomer nucleotides as substrates, and so these drugs are unable
to chain terminate host nucleic acid synthesis.
What is the key structural element that gives rise to this "clean" profile? - Answer-A
pseudoenantiomer of a natural nucleoside.
What is a pseudoenantiomer? - Answer-A pseudoenantiomer is a stereoisomer that is
not a true enantiomer because it isn't an exact mirror image usually hindered by steric
conformation.
Why does this feature make 3-TC so selective? - Answer-The pseudoenantiomer is
accepted by HIV reverse transcriptase and becomes incorporated into viral nucleic acid.
The drug acts like a chain terminator and stops nucleic acid replication. Because it is a
pseudoenantiomer, it will not be accepted as a substrate by host polymerases. Because
it does not inhibit any host enzymes or nucleic acid production, it does not produce a lot
of side effects.
What is meant by the term retrovirus? - Answer-Virus carries its genetic information in
the form of RNA. The RNA is translated into double stranded DNA inside the cell.
What is the key enzyme found in retroviruses that give rise to this behavior? - Answer-
Reverse transcriptase.
What general drug strategy is used to inhibit this enzyme? - Answer-Rational drug
design using chain termination and non-natural sugar nucleoside analogues.
What is the reaction of the process used to biosynthetically link isoprene units together?
- Answer-An SN2 reaction followed by an E1 reaction.
What is the source of most of the cholesterol in humans? - Answer-Made in the liver
from saturated and trans fats.
