Capped dipeptide alpha-ketoacid inhibitors of the HCV NS3 protease

Emanuela Nizi; Uwe Koch; Simona Ponzi; Victor G Matassa; Cristina Gardelli

doi:10.1016/s0960-894x(02)00691-1

Capped dipeptide alpha-ketoacid inhibitors of the HCV NS3 protease

Bioorg Med Chem Lett. 2002 Nov 18;12(22):3325-8. doi: 10.1016/s0960-894x(02)00691-1.

Authors

Emanuela Nizi¹, Uwe Koch, Simona Ponzi, Victor G Matassa, Cristina Gardelli

Affiliation

¹ Department of Chemistry, IRBM, MRL Rome, Via Pontina Km 30,600, Pomezia, 00040 Rome, Italy.

PMID: 12392743
DOI: 10.1016/s0960-894x(02)00691-1

Abstract

The N-terminal aminoacid of alpha-ketotripeptide inhibitors of the hepatitis C virus NS3 protease can be replaced with an alpha-hydroxy acid, leading to capped dipeptide inhibitors such as 20 with an IC(50) value of 3.0 microM. The importance of the lipophilic side chain interactions at S3 of the protease and the requirement of the capping residue with R configuration have been explained by molecular modeling studies.

MeSH terms

Binding Sites
Dipeptides / chemical synthesis
Dipeptides / pharmacology*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Keto Acids / chemistry*
Models, Molecular
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Dipeptides
Enzyme Inhibitors
Keto Acids
NS3 protein, hepatitis C virus
Viral Nonstructural Proteins