1. The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery.
- Author
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Kirkpatrick CL, Broberg CA, McCool EN, Lee WJ, Chao A, McConnell EW, Pritchard DA, Hebert M, Fleeman R, Adams J, Jamil A, Madera L, Strömstedt AA, Göransson U, Liu Y, Hoskin DW, Shaw LN, and Hicks LM
- Subjects
- Acinetobacter Infections drug therapy, Acinetobacter baumannii drug effects, Anti-Bacterial Agents pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Biological Products pharmacology, Cell Line, Tumor, Cyclotides pharmacology, Humans, Neoplasms drug therapy, Peptide Library, Anti-Bacterial Agents chemistry, Antineoplastic Agents, Phytogenic chemistry, Biological Products chemistry, Cyclotides chemistry, Drug Discovery, Viola chemistry
- 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.
- Published
- 2017
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