title: Enhanced dereplication of fungal cultures via use of mass defect filtering.
abstract: Effective and rapid dereplication is a hallmark of present-day drug discovery from natural sources. This project strove to both decrease the time and expand the structural diversity associated with dereplication methodologies. A 5 min liquid chromatographic run time employing heated electrospray ionization (HESI) was evaluated to determine whether it could be used as a faster alternative over the 10 min ESI method we reported previously. Results revealed that the 5 min method was as sensitive as the 10 min method and, obviously, was twice as fast. To facilitate dereplication, the retention times, UV absorption maxima, full-scan HRMS and MS/MS were cross-referenced with an in-house database of over 300 fungal secondary metabolites. However, this strategy was dependent upon the makeup of the screening in-house database. Thus, mass defect filtering (MDF) was explored as an additional targeted screening strategy to permit identification of structurally related components. The use of a dereplication platform incorporating the 5 min chromatographic method together with MDF facilitated rapid and effective identification of known compounds and detection of structurally related analogs in extracts of fungal cultures.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Noemi D
authors.initials: ND
authors.lastname: Paguigan
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Tamam
authors.initials: T
authors.lastname: El-Elimat
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Kao
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Huzefa A
authors.initials: HA
authors.lastname: Raja
authors.affiliation: Mycosynthetix, Hillsborough, NC, USA.
authors.forename: Cedric J
authors.initials: CJ
authors.lastname: Pearce
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
mesh_terms: D001688:Biological Products / Q000032:analysis / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D005658:Fungi / Q000378:metabolism*; D064210:Secondary Metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors
chemical_list: D001688:Biological Products