Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties
| Autor: | David J. Craik, Alysha G. Elliott, Yen-Hua Huang, Nicole Lawrence, Mark E. Cooper, Aurélie H. Benfield, Stephanie Chaousis, Olivier Cheneval, Sónia Troeira Henriques, Lai Yue Chan, Angela M. Kavanagh, Anjaneya S. Ravipati |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival 060110 Receptors and Membrane Biology anti fungal peptide 030403 Characterisation of Biological Macromolecules Lipid Bilayers Cell Antineoplastic Agents Peptide Pharmacology Biology 01 natural sciences Biochemistry anticancer peptide Cell membrane 03 medical and health sciences Anti-Infective Agents Cell Line Tumor medicine Animals Humans disulfide-rich peptide Mode of action Melanoma 060502 Infectious Agents chemistry.chemical_classification Leukemia Bacteria 010405 organic chemistry Fungi Spiders Bacterial Infections General Medicine host defence peptide Antimicrobial 3. Good health 0104 chemical sciences 030104 developmental biology medicine.anatomical_structure Mycoses 030406 Proteins and Peptides chemistry Drug development Cell culture peptide-lipid interactions Cancer cell Molecular Medicine Antimicrobial Cationic Peptides |
| Zdroj: | ACS Chemical Biology |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.7b00459 |
| Popis: | Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by ∼10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development. |
| Databáze: | OpenAIRE |
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