Donoghue

Question 1

Renin-Angiotensin System

Answer 1

Proteases Involved:

• Renin (Class: Aspartic acid protease, AA: Asp)
• ACE (Class: Metallo-protease, AA: His, X, Glu, Zn)

Angiotensinogen -> renin -> angiotensin 1 -> ace -> angiotensin 2 (acts on adrenal gland) -> aldosterone

*both for hypertension

Question 2

How is Angiotensin II formed?

Answer 2

ACE acts on Angiotensin I to form Angiotensin II

*look up what rxn is called

Question 3

Two Ways to Block Angiotensin II Formation

Answer 3

1. ) Inhibit Renin activity

2. ) Inhibit ACE activity

Question 4

HIV Proteases: Class & Role

Answer 4

Class: HIV-1 protease in class aspartic acid proteases

Role: HIV Protease processes gag and pol into functional proteins

Question 5

HIV Proteases: How Inhibitors Prevent Infection

Answer 5

Protease inhibitor drugs block the action of proteases. This prevents protease enzymes from doing their part in allowing HIV to multiply, interrupting the HIV life cycle.

HIV Protease is essential for viral replication
– Inhibiting this enzyme prevents polypeptide processing
– HIV PR inhibitors have a non-cleavable hydroxyethylene bond

Question 6

HIV Proteases: Why is Resistance Common?

Answer 6

HIV replication is error prone, causing mutations to occur. Mutations give a chance for the next generation to get an advantage. Many protease resistant strains emerge as a result.

Question 7

Protease Inhibitor Design

Answer 7

Transition State Mimic - almost always an alcohol (OH)