2024-03-28T15:51:11Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/86492019-08-30T11:25:43Zcom_10033_6855com_10033_6839col_10033_6856
Struck, F
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Collins, J
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2007-02-20T13:39:43Z
1994-05-25
2007-02-20T13:39:43Z
1994-05-25
Nucleic Acids Research 1994 22(10):1923-1924
0305-1048
1362-4962
7516066
http://hdl.handle.net/10033/8649
308097
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Simple and rapid 5' and 3' extension techniques in RT-PCR.
YES
2018-06-12T21:48:46Z
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Struck and Collins_final.pdf
free text from PubMed Central
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Struck and Collins_final.pdf.txt
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2019-08-30 11:25:43.312
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
oai:repository.helmholtz-hzi.de:10033/2666342019-08-30T11:28:51Zcom_10033_6855com_10033_6839col_10033_6856
Kügler, Jonas
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Schmelz, Stefan
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Gentzsch, Juliane
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Haid, Sibylle
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Pollmann, Erik
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van den Heuvel, Joop
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Franke, Raimo
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Pietschmann, Thomas
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Heinz, Dirk W
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Collins, John
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Research Group Directed Evolution, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany.
2013-01-23T10:44:47Z
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
2013-11-15T00:00:00Z
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.
ORIGINAL
Kügler et al_final.pdf
Kügler et al_final.pdf
submitted manuscript
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TEXT
Kügler et al_final.pdf.txt
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oai:hzi.openrepository.com:10033/266634
2019-08-30 11:28:51.5
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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