Solid phase synthesis of peptide aldehyde protease inhibitors. Probing the proteolytic sites of hepatitis C virus polyprotein.
The solid phase synthesis of a set of peptide aldehydes derived from the NS5A/NS5B junction of hepatitis C virus (HCV) viral polyprotein is demonstrated using an oxazolidine linker and the Multipin method. Deletion of the P6 and P5 residues results in a dramatic loss of inhibitory activity.
Ede
N J
NJ
Chiron Technologies Pty. Ltd., Clayton, Victoria , Australia. nick_ede@cc.chiron.com
Eagle
S N
SN
Wickham
G
G
Bray
A M
AM
Warne
B
B
Shoemaker
K
K
Rosenberg
S
S
D000447:Aldehydes / Q000138:chemical synthesis*; D010450:Endopeptidases / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D010455:Peptides / Q000138:chemical synthesis*; D020815:Polyproteins / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013053:Spectrophotometry; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000447:Aldehydes; D010450:Endopeptidases; D010455:Peptides; D020815:Polyproteins; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase