title: Capped dipeptide alpha-ketoacid inhibitors of the HCV NS3 protease.
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.
authors.affiliation: Department of Chemistry, IRBM, MRL Rome, Via Pontina Km 30,600, Pomezia, 00040 Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Nizi
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Simona
authors.initials: S
authors.lastname: Ponzi
authors.forename: Victor G
authors.initials: VG
authors.lastname: Matassa
authors.forename: Cristina
authors.initials: C
authors.lastname: Gardelli
mesh_terms: D001665:Binding Sites; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007651:Keto Acids / Q000737:chemistry*; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D004151:Dipeptides; D004791:Enzyme Inhibitors; D007651:Keto Acids; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases