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Isolation and chara...
Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
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- Abdurahman, Samir, 1965- (author)
- Karolinska Institutet
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- Végvári, Ákos (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Levi, Michael (author)
- Tripep AB, Huddinge, Sweden
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- Höglund, Stefan (author)
- Uppsala universitet,Institutionen för biokemi och organisk kemi,Department of Biochemistry, Uppsala University, Uppsala, Sweden
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- Högberg, Marita (author)
- Chemilia AB, Huddinge, Sweden
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- Tong, Weimin (author)
- Chemilia AB, Huddinge, Sweden
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- Romero, Ivan (author)
- Chemilia AB, Huddinge, Sweden
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- Balzarini, Jan (author)
- Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
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- Vahlne, Anders (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2009-04-08
- 2009
- English.
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In: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 6, s. 34-
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Abstract
Subject headings
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- Background: Formation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures. Results: Here we demonstrate that it is not G-NH2 itself but a metabolite thereof that displays antiviral activity. We show that conversion of G-NH2 to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2 metabolite was alpha-hydroxy-glycineamide (alpha-HGA). Chemically synthesized alpha-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2 which had no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized alpha-HGA further confirmed that the antiviral G-NH2-metabolite indeed was alpha-HGA. Conclusion: alpha-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, alpha-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering (hsv//eng)
Keyword
- Biology
- Biologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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