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Structure-activity ...
Structure-activity relationships for the selectivity of hepatitis C virus NS3 protease inhibitors
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- Poliakov, Anton (författare)
- Uppsala universitet,Institutionen för naturvetenskaplig biokemi
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- Johansson, Anja (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Åkerblom, Eva (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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Oscarsson, Karin (författare)
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Samuelsson, Bertil (författare)
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- Hallberg, Anders (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Danielson, Helena (författare)
- Uppsala universitet,Institutionen för naturvetenskaplig biokemi
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(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- Engelska.
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0304-4165. ; 1672:1, s. 51-59
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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