MCAT: Free Practice Quiz

HIV protease is an example of an aspartyl protease; an enzyme that utilizes an aspartate side chain during the catalytic cleavage of a peptide bond. Since HIV protease is a relatively small homodimer of a 99-residue protein, it can be directly synthesized, or cloned, and expressed in fast-growing cells. For this reason, it was targeted for structure-based drug design in order to treat HIV infection.

A portion of the peptide cleaved by HIV protease is shown in Figure 1.

Figure 1 The peptide bond cleaved by HIV protease

Using molecular models of the HIV protease enzyme, researchers designed and synthesized transition state analogs. One such molecule is Compound 1, shown in Figure 2, which is a potent HIV protease inhibitor.

Figure 2 Structure of Compound 1

Compound 1 has an in vivo half-life of 1.8 h and is primarily metabolized by CYP3A, an enzyme in the cytochrome P450 family. The major metabolite of Compound 1 results from the dealkylation of CH₂R groups attached to the piperazine ring system (Reaction 1).

Reaction 1

One of the main side effects of prolonged use of Compound 1 is the formation of kidney stones composed of calcium oxalate CaC₂O₄. Researchers used their knowledge of the HIV protease active site, and the metabolic pathways that lead to the destruction of Compound 1, to design and synthesize several derivatives of Compound 1 in an effort to modify its properties and increase its potency and half-life.

2. How many stereoisomers of Compound 1 exist?

HIV protease is an example of an aspartyl protease; an enzyme that utilizes an aspartate side chain during the catalytic cleavage of a peptide bond. Since HIV protease is a relatively small homodimer of a 99-residue protein, it can be directly synthesized, or cloned, and expressed in fast-growing cells. For this reason, it was targeted for structure-based drug design in order to treat HIV infection.

A portion of the peptide cleaved by HIV protease is shown in Figure 1.

Figure 1 The peptide bond cleaved by HIV protease

Using molecular models of the HIV protease enzyme, researchers designed and synthesized transition state analogs. One such molecule is Compound 1, shown in Figure 2, which is a potent HIV protease inhibitor.

Figure 2 Structure of Compound 1

Compound 1 has an in vivo half-life of 1.8 h and is primarily metabolized by CYP3A, an enzyme in the cytochrome P450 family. The major metabolite of Compound 1 results from the dealkylation of CH₂R groups attached to the piperazine ring system (Reaction 1).

Reaction 1

One of the main side effects of prolonged use of Compound 1 is the formation of kidney stones composed of calcium oxalate CaC₂O₄. Researchers used their knowledge of the HIV protease active site, and the metabolic pathways that lead to the destruction of Compound 1, to design and synthesize several derivatives of Compound 1 in an effort to modify its properties and increase its potency and half-life.

1. Compound 1 is used to treat HIV infection based on its ability to act as:

HIV protease is an example of an aspartyl protease; an enzyme that utilizes an aspartate side chain during the catalytic cleavage of a peptide bond. Since HIV protease is a relatively small homodimer of a 99-residue protein, it can be directly synthesized, or cloned, and expressed in fast-growing cells. For this reason, it was targeted for structure-based drug design in order to treat HIV infection.

A portion of the peptide cleaved by HIV protease is shown in Figure 1.

Figure 1 The peptide bond cleaved by HIV protease

Using molecular models of the HIV protease enzyme, researchers designed and synthesized transition state analogs. One such molecule is Compound 1, shown in Figure 2, which is a potent HIV protease inhibitor.

Figure 2 Structure of Compound 1

Compound 1 has an in vivo half-life of 1.8 h and is primarily metabolized by CYP3A, an enzyme in the cytochrome P450 family. The major metabolite of Compound 1 results from the dealkylation of CH₂R groups attached to the piperazine ring system (Reaction 1).

Reaction 1

One of the main side effects of prolonged use of Compound 1 is the formation of kidney stones composed of calcium oxalate CaC₂O₄. Researchers used their knowledge of the HIV protease active site, and the metabolic pathways that lead to the destruction of Compound 1, to design and synthesize several derivatives of Compound 1 in an effort to modify its properties and increase its potency and half-life.

3. Why do kidney stones form in some individuals treated with Compound 1?

HIV protease is an example of an aspartyl protease; an enzyme that utilizes an aspartate side chain during the catalytic cleavage of a peptide bond. Since HIV protease is a relatively small homodimer of a 99-residue protein, it can be directly synthesized, or cloned, and expressed in fast-growing cells. For this reason, it was targeted for structure-based drug design in order to treat HIV infection.

A portion of the peptide cleaved by HIV protease is shown in Figure 1.

Figure 1 The peptide bond cleaved by HIV protease

Using molecular models of the HIV protease enzyme, researchers designed and synthesized transition state analogs. One such molecule is Compound 1, shown in Figure 2, which is a potent HIV protease inhibitor.

Figure 2 Structure of Compound 1

Compound 1 has an in vivo half-life of 1.8 h and is primarily metabolized by CYP3A, an enzyme in the cytochrome P450 family. The major metabolite of Compound 1 results from the dealkylation of CH₂R groups attached to the piperazine ring system (Reaction 1).

Reaction 1

One of the main side effects of prolonged use of Compound 1 is the formation of kidney stones composed of calcium oxalate CaC₂O₄. Researchers used their knowledge of the HIV protease active site, and the metabolic pathways that lead to the destruction of Compound 1, to design and synthesize several derivatives of Compound 1 in an effort to modify its properties and increase its potency and half-life.

4. The peptide bond between which two amino acid residues is cleaved by HIV protease?

Organic acids, denoted by HA, are only minimally deprotonated when added to pure water.

HA(aq)  H⁺(aq) + A^–(aq)

When dissolved in the blood, however, HA fully dissociate. What factor can be used to explain this discrepancy?

In oxidative phosphorylation, cytochrome c acts as:

Which primer is most suitable for PCR?

In which phase of meiosis does nondisjunction occur?

Yeast cells can grow under either aerobic or anaerobic conditions. If the same concentration of glucose were used to grow two different yeast colonies, would the growth rate be faster under aerobic or anaerobic conditions?

If the GAPDH gene is continuously expressed, where is it most likely found?