Search: L773:0006 3002 OR L773:0304 4165 >
Structure-activity ...
Structure-activity relationships for the selectivity of hepatitis C virus NS3 protease inhibitors
-
- Poliakov, Anton (author)
- Uppsala universitet,Institutionen för naturvetenskaplig biokemi
-
- Johansson, Anja (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
-
- Åkerblom, Eva (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
-
show more...
-
Oscarsson, Karin (author)
-
Samuelsson, Bertil (author)
-
- Hallberg, Anders (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
-
- Danielson, Helena (author)
- Uppsala universitet,Institutionen för naturvetenskaplig biokemi
-
show less...
-
(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- English.
-
In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0304-4165. ; 1672:1, s. 51-59
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- The selectivity of hepatitis C virus (HCV) non-structural protein 3 (NS3) protease inhibitors was determined by evaluating their inhibitory effect on other serine proteases (human leukocyte elastase (HLE), porcine pancreatic elastase (PPE), bovine pancreatic chymotrypsin (BPC)) and a cysteine protease (cathepsin B). For these peptide inhibitors, the P1-side chain and the C-terminal group were the major determinants of selectivity. Inhibitors with electrophilic C-terminal residues were generally non-selective while compounds with non-electrophilic C-terminal residues were more selective. Furthermore, compounds with P1 aminobutyric acid residues were non-selective, while 1-aminocyclopropane-1-carboxylic acid (ACPC) and norvaline-based inhibitors were generally selective. The most potent and selective inhibitors of NS3 protease tested contained a non-electrophilic phenyl acyl sulfonamide C-terminal residue. HLE was most likely to be inhibited by the HCV protease inhibitors, in agreement with similar substrate specificities for these enzymes. The identified structure-activity relationships for selectivity are of significance for design of selective HCV NS3 protease inhibitors.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Hepacivirus/chemistry/*enzymology/metabolism
- Protease Inhibitors/*pharmacology
- Research Support; Non-U.S. Gov't
- Structure-Activity Relationship
- Viral Nonstructural Proteins/antagonists & inhibitors/*chemistry/*metabolism
- Biochemistry
- Biokemi
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database