PROTEASE INHIBITORS STRUCTURES

Question 1

Answer 1

SAQUINAVIR (ROCHE)

High MW

Extremely potent

Goals to design drug: Reduce MW, reduce peptide

chracter, use crystal structure to guide development,

5 sub-sites occupied

Hydrogen bonding between hydroxyethylamine and Asp residues

Question 2

Answer 2

RITONAVIR

Same goal as SAquinavir

They used symmetry in catalytic site

Replaced bound water with an actual functional group.

Question 3

Answer 3

INDINAVIR

Question 4

Answer 4

NELFINAVIR

Question 5

Answer 5

PALINAVIR

Inhibits both HIV-1 and HIV-2 proteases

Left side similar to Saquinavine

Keep C=O binding to water molecule

Question 6

Answer 6

TIPRANAVIR

Not a peptide like protease inhibitor

It binds active site of protease

Less Resistance because of different scaffold

Question 7

Answer 7

2nd Generation Protease Inhibitors

Designed to deal with resistance

Amprenavir

Darunavir

Reduction of Peptide Character

Enhanced solubility

Reduced number of Assymetric centers