HIV-1 Protease Inhibitors Overview

HIV-1 Protease Inhibitors

• HIV-1 protease inhibitors are used to treat HIV-1 infections and prevent the onset of AIDS.
• HIV-1 protease inhibitors work by blocking the activity of HIV-1 protease, an enzyme that is essential for the replication of the virus.
• HIV-1 mutants can develop resistance to protease inhibitors, necessitating the development of new inhibitors.
• Compound 1 is a new HIV-1 protease inhibitor being tested.
• Compound 1 has a Ki value of 60.3 μM, which indicates its binding affinity to HIV-1 protease.
• Ki is the dissociation constant for the enzyme-bound inhibitor, which can be EI or ESI depending on the type of inhibitor.
• HIV-1 protease cleaves the peptide bond after leucine and before phenylalanine in the peptide substrate IRKILFLDG.
• The study investigates the kinetics of HIV-1 protease with and without Compound 1.
• Michaelis-Menten kinetics is followed by HIV-1 protease.
• A Lineweaver-Burk plot of Vo-1 versus [S]-1 (without Compound 1) and at different Compound 1 concentrations produces parallel straight lines with positive slopes, signifying competitive inhibition.

Preparation of Compound 1 Solution

• To prepare 100 mL of a solution with a concentration equal to Ki (60.3 μM), 2.92 mg of Compound 1 is required.
• The calculation involves converting 60.3 μM to μmol, then to mol, and finally multiplying by the molar mass of Compound 1 (483.5 g/mol) to obtain the mass in grams (0.00292 g).

HIV-1 Protease Inhibitors

• HIV-1 protease inhibitors are effective in reducing HIV-1 levels and delaying AIDS onset
• HIV-1 mutants are developing resistance to existing protease inhibitors
• Compound 1 is a new protease inhibitor being tested

Compound 1

• Compound 1 has a molecular weight of 483.5 g/mol
• Compound 1 inhibits HIV-1 protease with a Ki of 60.3 μM
• Ki is the dissociation constant for the enzyme-bound inhibitor
• The peptide substrate for HIV-1 protease is IRKILFLDG
• HIV-1 protease hydrolyzes the peptide bond after leucine and before phenylalanine

Kinetic Parameters

• The data was analyzed using Michaelis-Menten kinetics
• A Lineweaver-Burk plot was used to determine the kinetic parameters
• The plot showed parallel straight lines with positive slopes
• This pattern suggests that Compound 1 is a competitive inhibitor

Calculating the Amount of Compound 1 Needed

• To prepare 100.00 mL of solution with a concentration equal to Ki (60.3 μM), 2.92 mg of Compound 1 is required
• You can calculate this using the Molarity equation: M = mol of solute/ L
• Convert 100 ml to L (100 ml / 1000 mL/L = 0.1 L)
• Plug the values into the equation ( 60.3 μmol / 0.1 L)
• Convert μmol to mol and then multiply by the molecular weight (483.5 g/mol) to get the mass in grams