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Enhanced dereplication of fungal cultures via use of mass defect filtering

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 ion...

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Detalles Bibliográficos
Autores principales: Paguigan, Noemi D, El-Elimat, Tamam, Kao, Diana, Raja, Huzefa A, Pearce, Cedric J, Oberlies, Nicholas H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407915/
https://www.ncbi.nlm.nih.gov/pubmed/28074050
http://dx.doi.org/10.1038/ja.2016.145
Descripción
Sumario: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.