PepSAVI-MS Reveals a Proline-rich Antimicrobial Peptide in Amaranthus tricolor
| Autor: | Lilian R. Heil, Andrew J. Wommack, Tessa B. Moyer, Dennis Goldfarb, Christine L. Kirkpatrick, Nicole C. Parsley, William A Lefever, Leslie M. Hicks |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
chemistry.chemical_classification 010405 organic chemistry Chemistry Organic Chemistry Antimicrobial peptides Pharmaceutical Science Peptide medicine.disease_cause Antimicrobial 01 natural sciences 0104 chemical sciences Analytical Chemistry Hydroxylation 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Complementary and alternative medicine Biochemistry Drug Discovery medicine Molecular Medicine Proline Isoleucine Leucine Escherichia coli |
| Zdroj: | Journal of Natural Products. 82:2744-2753 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.9b00352 |
| Popis: | Traditional medicinal plants are a rich source of antimicrobials; however, the bioactive peptide constituents of most ethnobotanical species remain largely unexplored. Herein, PepSAVI-MS, a mass spectrometry-based peptidomics pipeline, was implemented for antimicrobial peptide (AMP) discovery in the medicinal plant Amaranthus tricolor. This investigation revealed a novel 1.7 kDa AMP with strong activity against Escherichia coli ATCC 25922, deemed Atr-AMP1. Initial efforts to determine the sequence of Atr-AMP1 utilized chemical derivatization and enzymatic digestion to provide information about specific residues and post-translational modifications. EThcD (electron-transfer/higher-energy collision dissociation) produced extensive backbone fragmentation and facilitated de novo sequencing, the results of which were consistent with orthogonal characterization experiments. Additionally, multistage HCD (higher-energy collisional dissociation) facilitated discrimination between isobaric leucine and isoleucine. These results revealed a positively charged proline-rich peptide present in a heterogeneous population of multiple peptidoforms, possessing several post-translational modifications including a disulfide bond, methionine oxidation, and proline hydroxylation. Additional bioactivity screening of a simplified fraction containing Atr-AMP1 revealed activity against Staphylococcus aureus LAC, demonstrating activity against both a Gram-negative and a Gram-positive bacterial species unlike many known short chain proline-rich antimicrobial peptides. |
| Databáze: | OpenAIRE |
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