Passage 1 (Questions 1-4) Human immunodeficiency virus 1 (HIV-1) protease inhibitors have been successful at lowering HIV-1 levels and blocking the onset of acquired immune deficiency syndrome (AIDS). However, because HIV-1 mutants are developing resistance to current protease inhibitors, new inhibitors such as Compound 1 (molar mass: 483.5 g.mol-¹) are being tested. Compound 1 Compound 1 has been shown to inhibit HIV-1 protease with K, = 60.3 μM (Table 1). K; is the dissociation constant for the enzyme-bound inhibitor, which is either El or ESI, depending on the type of inhibitor. The peptide substrate for HIV-1 protease is IRKILFLDG. HIV-1 protease hydrolyzes only the peptide bond after leucine and before phenylalanine. Compound 1 (μm) Table 1 Kinetic Parameters of HIV-1 Protease with and without Compound 1 10 60.0 120 H 00.149 0.832 0.126 0.151 60.3 0.430 0.064 0.149 60.3 Note: HIV-1 protease follows Michaelis-Menten kinetics. FN A Lineweaver-Burk plot of V.¹ versus [S]-¹, both without Compound 1 and with different concentrations of Compound 1, generates a set of parallel straight lines with positive slopes. K₁ KM Kcat KM (MM) (S¹) (mM-¹ s¹) (UM) 1.678 0.250 Adapted from T. Sperka, J. Pitlik, P. Bagossi, and J. Tösner, Bioorganic & Medicinal Chemistry Letters. ©2005 Elsevier Inc. Question 2 If only [1] is increased, then [ESI] or [El] increases. This is an example of: O A. the Bose-Einstein Principle. OB. the Heisenberg Uncertainty Principle. OC. the Le Châtelier's Principle. O D. the Pauli Exclusion Principle. Question 3 Which structural change to Compound 1 would make it more water soluble? O A. 33.5 and 15.7 O A. Replacing benzene CH with N in the ring OB. Replacing C=0 with C=CH₂ OC. Replacing N-N-N with CH-CH=CH O D. Replacing NH with NCH3 OB. 75 and 30.1 Question 4 In μM-s¹ and μM, what should the approximate values of kcat/KM and K, be, respectively, when [1] = 180 µM? O c. 150 and 60.3 O D. 300 and 120.6 Question 1 What quantity of Compound 1 must be provided to prepare 100.00 mL of solution with a concentration equal to K₁? OA. 48.4 mg OB. 24.2 mg O c. 5.64 mg OD. 2.92 mg

Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
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Passage 1 (Questions 1-4)
Human immunodeficiency virus 1 (HIV-1) protease inhibitors have been
successful at lowering HIV-1 levels and blocking the onset of acquired
immune deficiency syndrome (AIDS). However, because HIV-1 mutants
are developing resistance to current protease inhibitors, new inhibitors
such as Compound 1 (molar mass: 483.5 g.mol-¹) are being tested.
Compound 1
Compound 1 has been shown to inhibit HIV-1 protease with K₁ = 60.3
μM (Table 1). K; is the dissociation constant for the enzyme-bound
inhibitor, which is either El or ESI, depending on the type of inhibitor. The
peptide substrate for HIV-1 protease is IRKILFLDG. HIV-1 protease
hydrolyzes only the peptide bond after leucine and before
phenylalanine.
Table 1 Kinetic Parameters of HIV-1 Protease with and without
Compound 1
Compound 1
(μM)
K₁
KM Kcat Км
(mm) (¹) (mM-¹ s¹) (HM)
00.149
1.678 0.250
0.832 0.126 0.151 60.3
0.149 60.3
0.430 0.064
Note: HIV-1 protease follows Michaelis-Menten kinetics.
0
60.0
120
H
A Lineweaver-Burk plot of V.¹ versus [S]-1, both without Compound 1
and with different concentrations of Compound 1, generates a set of
parallel straight lines with positive slopes.
Adapted from T. Sperka, J. Pitlik, P. Bagossi, and J. Tösner, Bioorganic & Medicinal Chemistry Letters. ©2005
Elsevier Inc.
Question 2
If only [1] is increased, then [ESI] or [El] increases. This is an example of:
O A. the Bose-Einstein Principle.
OB. the Heisenberg Uncertainty Principle.
O c. the Le Châtelier's Principle.
O D. the Pauli Exclusion Principle.
-
Question 3
Which structural change to Compound 1 would make it more water
soluble?
O A. Replacing benzene CH with N in the ring
OB. Replacing C=0 with C=CH₂
O c. Replacing N-N-N with CH-CH=CH
OD. Replacing NH with NCH3
OA. 33.5 and 15.7
O B. 75 and 30.1
Question 4
In μM.s¹ and μM, what should the approximate values of keat/KM and
K be, respectively, when [1] = 180 µM?
O C. 150 and 60.3
O D. 300 and 120.6
Question 1
What quantity of Compound 1 must be provided to prepare 100.00 mL
of solution with a concentration equal to K;?
OA. 48.4 mg
O B. 24.2 mg
O c. 5.64 mg
OD. 2.92 mg
Transcribed Image Text:Passage 1 (Questions 1-4) Human immunodeficiency virus 1 (HIV-1) protease inhibitors have been successful at lowering HIV-1 levels and blocking the onset of acquired immune deficiency syndrome (AIDS). However, because HIV-1 mutants are developing resistance to current protease inhibitors, new inhibitors such as Compound 1 (molar mass: 483.5 g.mol-¹) are being tested. Compound 1 Compound 1 has been shown to inhibit HIV-1 protease with K₁ = 60.3 μM (Table 1). K; is the dissociation constant for the enzyme-bound inhibitor, which is either El or ESI, depending on the type of inhibitor. The peptide substrate for HIV-1 protease is IRKILFLDG. HIV-1 protease hydrolyzes only the peptide bond after leucine and before phenylalanine. Table 1 Kinetic Parameters of HIV-1 Protease with and without Compound 1 Compound 1 (μM) K₁ KM Kcat Км (mm) (¹) (mM-¹ s¹) (HM) 00.149 1.678 0.250 0.832 0.126 0.151 60.3 0.149 60.3 0.430 0.064 Note: HIV-1 protease follows Michaelis-Menten kinetics. 0 60.0 120 H A Lineweaver-Burk plot of V.¹ versus [S]-1, both without Compound 1 and with different concentrations of Compound 1, generates a set of parallel straight lines with positive slopes. Adapted from T. Sperka, J. Pitlik, P. Bagossi, and J. Tösner, Bioorganic & Medicinal Chemistry Letters. ©2005 Elsevier Inc. Question 2 If only [1] is increased, then [ESI] or [El] increases. This is an example of: O A. the Bose-Einstein Principle. OB. the Heisenberg Uncertainty Principle. O c. the Le Châtelier's Principle. O D. the Pauli Exclusion Principle. - Question 3 Which structural change to Compound 1 would make it more water soluble? O A. Replacing benzene CH with N in the ring OB. Replacing C=0 with C=CH₂ O c. Replacing N-N-N with CH-CH=CH OD. Replacing NH with NCH3 OA. 33.5 and 15.7 O B. 75 and 30.1 Question 4 In μM.s¹ and μM, what should the approximate values of keat/KM and K be, respectively, when [1] = 180 µM? O C. 150 and 60.3 O D. 300 and 120.6 Question 1 What quantity of Compound 1 must be provided to prepare 100.00 mL of solution with a concentration equal to K;? OA. 48.4 mg O B. 24.2 mg O c. 5.64 mg OD. 2.92 mg
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