2024-03-28T18:29:31Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/86492019-08-30T11:25:43Zcom_10033_6855com_10033_6839col_10033_6856
Helmholtz Zentrum für Infektionsforschung Repository
author
Struck, F
author
Collins, J
2007-02-20T13:39:43Z
1994-05-25
Nucleic Acids Research 1994 22(10):1923-1924
0305-1048
7516066
http://hdl.handle.net/10033/8649
308097
Images
en_US
Simple and rapid 5' and 3' extension techniques in RT-PCR.
URL
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Struck and Collins_final.pdf.txt
oai:repository.helmholtz-hzi.de:10033/2666342019-08-30T11:28:51Zcom_10033_6855com_10033_6839col_10033_6856
Helmholtz Zentrum für Infektionsforschung Repository
author
Kügler, Jonas
author
Schmelz, Stefan
author
Gentzsch, Juliane
author
Haid, Sibylle
author
Pollmann, Erik
author
van den Heuvel, Joop
author
Franke, Raimo
author
Pietschmann, Thomas
author
Heinz, Dirk W
author
Collins, John
department
Research Group Directed Evolution, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany.
2013-01-23T10:44:47Z
2012-11-09
High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease refractory to common resistant mutants. 2012, 287 (46):39224-32 J. Biol. Chem.
1083-351X
22965230
10.1074/jbc.M112.393843
http://hdl.handle.net/10033/266634
The Journal of biological chemistry
Hepatitis C virus (HCV) NS3-4A protease is essential for viral replication. All current small molecular weight drugs against NS3-4A are substrate peptidomimetics that have a similar binding and resistance profile. We developed inhibitory peptides (IPs) capping the active site and binding via a novel "tyrosine" finger at an alternative NS3-4A site that is of particular interest for further HCV drug development. The peptides are not cleaved due to a combination of geometrical constraints and impairment of the oxyanion hole function. Selection and optimization through combinatorial phagemid display, protein crystallography, and further modifications resulted in a 32-amino acid peptide with a K(i) of 0.53 nm. Inhibition of viral replication in cell culture was demonstrated by fusion to a cell-penetrating peptide. Negligible susceptibility to known (A156V and R155K) resistance mutations of the NS3-4A protease was observed. This work shows for the first time that antiviral peptides can target an intracellular site and reveals a novel druggable site on the HCV protease.
en
Archived with thanks to The Journal of biological chemistry
High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease refractory to common resistant mutants.
Article
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Kügler et al_final.pdf.txt