Publication:
Competitive inhibition of the dengue virus NS3 serine protease by synthetic peptides representing polyprotein cleavage sites

dc.contributor.authorSantad Chanprapaphen_US
dc.contributor.authorPatchreenart Saparpakornen_US
dc.contributor.authorChak Sangmaen_US
dc.contributor.authorPornwaratt Niyomrattanakiten_US
dc.contributor.authorSupa Hannongbuaen_US
dc.contributor.authorChanan Angsuthanasombaten_US
dc.contributor.authorGerd Katzenmeieren_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherKasetsart Universityen_US
dc.date.accessioned2018-06-21T08:09:25Z
dc.date.available2018-06-21T08:09:25Z
dc.date.issued2005-05-20en_US
dc.description.abstractThe NS3 serine protease of dengue virus is required for the maturation of the viral polyprotein and consequently represents a promising target for the development of antiviral inhibitors. However, the substrate specificity of this enzyme has been characterized only to a limited extent. In this study, we have investigated product inhibition of the NS3 protease by synthetic peptides derived from the P6-P1 and the P1′-P5′ regions of the natural polyprotein substrate. N-terminal cleavage site peptides corresponding to the P6-P1 region of the polyprotein were found to act as competitive inhibitors of the enzyme with Kivalues ranging from 67 to 12 μM. The lowest Kivalue was found for the peptide representing the NS2A/NS2B cleavage site, RTSKKR. Inhibition by this cleavage site sequence was analyzed by using shorter peptides, SKKR, KKR, KR, AGRR, and GKR. With the exception of the peptide AGRR which did not inhibit the protease at a concentration of 1 mM, all other peptides displayed Kivalues in the range from 188 to 22 μM. Peptides corresponding to the P1′-P5′ region of the polyprotein cleavage sites had no effect on enzymatic activity at a concentration of 1 mM. Molecular docking data of peptide inhibitors to a homology-based model of the dengue virus type 2 NS2B(H)-NS3p co-complex indicate that binding of the non-prime site product inhibitors is similar to ground-state binding of the corresponding substrates. © 2005 Elsevier Inc. All rights reserved.en_US
dc.identifier.citationBiochemical and Biophysical Research Communications. Vol.330, No.4 (2005), 1237-1246en_US
dc.identifier.doi10.1016/j.bbrc.2005.03.107en_US
dc.identifier.issn0006291Xen_US
dc.identifier.other2-s2.0-17044395894en_US
dc.identifier.urihttps://repository.li.mahidol.ac.th/handle/20.500.14594/16345
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=17044395894&origin=inwarden_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleCompetitive inhibition of the dengue virus NS3 serine protease by synthetic peptides representing polyprotein cleavage sitesen_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=17044395894&origin=inwarden_US

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