Cyclization of the Antimicrobial Peptide Gomesin with Native Chemical Ligation: Influences on Stability and Bioactivity
Abstract
Gomesin is an 18‐residue peptide originally isolated from the hemocytes of the Brazilian spider Acanthoscurria gomesiana. A broad spectrum of bioactivities have been attributed to gomesin, including in vivo and in vitro cytotoxicity against tumour cells, antimicrobial, antifungal, anti‐Leishmania and antimalarial effects. Given the potential therapeutic applications of gomesin, it was of interest to determine if an engineered version with a cyclic backbone has improved stability and bioactivity. Cyclization has been shown to confer enhanced stability and activity to a range of bioactive peptides and, in the case of a cone snail venom peptide, confer oral activity in a pain model. The current study demonstrates that cyclization improves the in vitro stability of gomesin over a 24 hour time period and enhances cytotoxicity against a cancer cell line without being toxic to a noncancerous cell line. In addition, antimalarial activity is enhanced upon cyclization. These findings provide additional insight into the influences of backbone cyclization on the therapeutic potential of peptides.
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- Authors
- Chan, L. Y., Zhang, V. M., Huang, Y., Waters, N. C., Bansal, P. S., Craik, D. J., & Daly, N. L.
- Affiliations
- The University of Queensland (AU)
- Australian Nuclear Science and Technology Organisation (AU)
- Corresponding author
- Daly, Norelle L.
- Venue
- ChemBioChem
- Publisher
- Wiley
- Published
- 2013-02-20
- Volume
- 14
- Issue
- 5
- Pages
- 617-624
- ISSN
- 1439-4227 (ISSN-L)
- 1439-7633
- OpenAlex
- W2067337286
- Cited by
- 88
- References
- 46
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 5 · 2023: 5 · 2022: 15 · 2021: 3 · 2020: 12 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 3
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ChemBioChem (publishedVersion)
- PubMed (publishedVersion)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- gomesin, antimicrobial peptides, peptide cyclization, native chemical ligation, spider venom peptides, peptide stability, cytotoxicity, antimalarial activity, antifungal activity
- MeSH terms
- Amino Acid Sequence, Animals, Anti-Infective Agents, Antimalarials, Cell Membrane, Cyclization, HeLa Cells, Humans, Molecular Sequence Data, Spiders, Sequence Alignment, Protein Structure, Secondary, Antimicrobial Cationic Peptides, Cell Line, Tumor, Protein Stability
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