Show simple item record

dc.contributor.authorXie, Yan
dc.contributor.authorFeng, Yunjiang
dc.contributor.authorDi Capua, Angela
dc.contributor.authorMak, Tin
dc.contributor.authorBuchko, Garry W
dc.contributor.authorMyler, Peter J
dc.contributor.authorLiu, Miaomiao
dc.contributor.authorQuinn, Ronald J
dc.date.accessioned2020-03-12T04:29:29Z
dc.date.available2020-03-12T04:29:29Z
dc.date.issued2020
dc.identifier.issn1660-3397
dc.identifier.doi10.3390/md18030149
dc.identifier.urihttp://hdl.handle.net/10072/392303
dc.description.abstractIn recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods in drug discovery. The PhenoTarget approach combines the strengths of the PDD and TDD approaches. Phenotypic screening is conducted initially to detect cellular active components and the hits are then screened against a panel of putative targets. This PhenoTarget protocol can be equally applied to pure compound libraries as well as natural product fractions. Here we described the use of the PhenoTarget approach to identify an anti-tuberculosis lead compound. Fractions from Polycarpa aurata were identified with activity against Mycobacterium tuberculosis H37Rv. Native magnetic resonance mass spectrometry (MRMS) against a panel of 37 proteins from Mycobacterium proteomes showed that a fraction from a 95% ethanol re-extraction specifically formed a protein-ligand complex with Rv1466, a putative uncharacterized Mycobacterium tuberculosis protein. The natural product responsible was isolated and characterized to be polycarpine. The molecular weight of the ligand bound to Rv1466, 233 Da, was half the molecular weight of polycarpine less one proton, indicating that polycarpine formed a covalent bond with Rv1466
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.relation.ispartofpagefrom149
dc.relation.ispartofpageto149
dc.relation.ispartofissue3
dc.relation.ispartofjournalMarine Drugs
dc.relation.ispartofvolume18
dc.subject.fieldofresearchPhysical Chemistry (incl. Structural)
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode0306
dc.subject.fieldofresearchcode1115
dc.subject.keywordsMRMS
dc.subject.keywordsPhenoTarget approach
dc.subject.keywordspolycarpine
dc.subject.keywordsprotein-ligand complex
dc.titleA Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationXie, Y; Feng, Y; Di Capua, A; Mak, T; Buchko, GW; Myler, PJ; Liu, M; Quinn, RJ, A Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466., Marine Drugs, 2020, 18 (3), pp. 149-149
dcterms.dateAccepted2020-02-20
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-03-12T04:20:47Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© Author(s) 2020. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorQuinn, Ronald J.
gro.griffith.authorFeng, Yun J.
gro.griffith.authorXie, Yan
gro.griffith.authorLiu, Miaomiao
gro.griffith.authorMak, Tin
gro.griffith.authorDi Capua, Angela


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record