Show simple item record

dc.contributor.authorCheng, Nancy
dc.contributor.authorLee, Sook-Kyung
dc.contributor.authorDonover, P. Scott
dc.contributor.authorReichman, Mel
dc.contributor.authorSchiffer, Celia A.
dc.contributor.authorHull-Ryde, Emily A.
dc.contributor.authorSwanstrom, Ronald I.
dc.contributor.authorJanzen, William P.
dc.date2022-08-11T08:08:00.000
dc.date.accessioned2022-08-23T15:39:03Z
dc.date.available2022-08-23T15:39:03Z
dc.date.issued2013-12-04
dc.date.submitted2015-01-09
dc.identifier.citationJ Lab Autom. 2013 Dec 4;19(3):297-303. <a href="http://dx.doi.org/10.1177/2211068213513453">Link to article on publisher's site</a>
dc.identifier.issn2211-0682 (Electronic)
dc.identifier.doi10.1177/2211068213513453
dc.identifier.pmid24305957
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26071
dc.description.abstractCurrent antiretroviral treatments target multiple pathways important for human immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and integration of the DNA provirus, and the processing of viral polyprotein precursors. However, HIV is becoming increasingly resistant to these "combination therapies." Recent findings show that inhibition of HIV Gag protein cleavage into its two structural proteins, matrix (MA) and capsid (CA), has a devastating effect on viral production, revealing a potential new target class for HIV treatment. Unlike the widely used HIV protease inhibitors, this new class of inhibitor would target the substrate, not the protease enzyme itself. This approach offers a distinct advantage in that inhibitors of MA/CA would only need to affect a subset of the Gag molecules to disable viral replication. To discover MA/CA-specific inhibitors, we constructed a modified MA/CA fusion peptide (MA/CADelta) that contains the HIV protease (PR) cleavage site as well as a tetracysteine motif for fluorescent labeling. The HIV PR cleavage of MA/CADelta can then be monitored via fluorescence polarization (FP). We have adapted this FP assay for high-throughput screening and validated it according to industry standards using a 384-well plate format. We have currently tested 24,000 compounds in this assay and here detail the screening methodology and the results of this screening campaign.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24305957&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1177/2211068213513453
dc.subjectBiochemistry
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectLaboratory and Basic Science Research
dc.subjectMedicinal Chemistry and Pharmaceutics
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectMolecular Biology
dc.subjectPharmacology
dc.subjectTherapeutics
dc.titleDevelopment of a Novel Screening Strategy Designed to Discover a New Class of HIV Drugs
dc.typeJournal Article
dc.source.journaltitleJournal of laboratory automation
dc.source.volume19
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/bmp_pp/209
dc.identifier.contextkey6515358
html.description.abstract<p>Current antiretroviral treatments target multiple pathways important for human immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and integration of the DNA provirus, and the processing of viral polyprotein precursors. However, HIV is becoming increasingly resistant to these "combination therapies." Recent findings show that inhibition of HIV Gag protein cleavage into its two structural proteins, matrix (MA) and capsid (CA), has a devastating effect on viral production, revealing a potential new target class for HIV treatment. Unlike the widely used HIV protease inhibitors, this new class of inhibitor would target the substrate, not the protease enzyme itself. This approach offers a distinct advantage in that inhibitors of MA/CA would only need to affect a subset of the Gag molecules to disable viral replication. To discover MA/CA-specific inhibitors, we constructed a modified MA/CA fusion peptide (MA/CADelta) that contains the HIV protease (PR) cleavage site as well as a tetracysteine motif for fluorescent labeling. The HIV PR cleavage of MA/CADelta can then be monitored via fluorescence polarization (FP). We have adapted this FP assay for high-throughput screening and validated it according to industry standards using a 384-well plate format. We have currently tested 24,000 compounds in this assay and here detail the screening methodology and the results of this screening campaign.</p>
dc.identifier.submissionpathbmp_pp/209
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages297-303


This item appears in the following Collection(s)

Show simple item record