title: The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery.
abstract: The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Kirkpatrick
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Broberg
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Elijah N
authors.initials: EN
authors.lastname: McCool
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Chao
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Evan W
authors.initials: EW
authors.lastname: McConnell
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Pritchard
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Hebert
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida , Tampa, Florida, United States.
authors.forename: Renee
authors.initials: R
authors.lastname: Fleeman
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida , Tampa, Florida, United States.
authors.forename: Jessie
authors.initials: J
authors.lastname: Adams
authors.affiliation: Department of Biochemistry, University of Agriculture Faisalabad , Faisalabad, Pakistan.
authors.forename: Amer
authors.initials: A
authors.lastname: Jamil
authors.affiliation: Department of Pathology, Dalhousie University , Halifax, Nova Scotia, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Madera
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Uppsala, Sweden.
authors.forename: Adam A
authors.identifier: 0000-0001-9070-6944
authors.initials: AA
authors.lastname: Strömstedt
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University , Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Göransson
authors.affiliation: Department of Statistics and Operations Research, Department of Genetics, Department of Biostatistics, and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Dalhousie University , Halifax, Nova Scotia, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Hoskin
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida , Tampa, Florida, United States.
authors.forename: Lindsey N
authors.identifier: 0000-0002-0629-8990
authors.initials: LN
authors.lastname: Shaw
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, United States.
authors.forename: Leslie M
authors.identifier: 0000-0002-8008-3998
authors.initials: LM
authors.lastname: Hicks
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy; D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D047169:Cyclotides / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D019151:Peptide Library; D032413:Viola / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D047169:Cyclotides; D019151:Peptide Library; C473355:cycloviolacin O2