Abstract
A series of amino-terminal truncated analogues of quail antimicrobial peptide Cc-CATH3(1-29) were created and examined antibacterial activity against Gram-positive bacteria, cytotoxicity against mouse fibroblast cell line, and membrane perturbation activity against various membrane models. Parent peptide Cc-CATH3(1-29) and the first four-residue truncated peptide Cc-CATH3(5-29) were active in all tested experiments. In contrast, the eight- and twelve-residue truncated variants Cc-CATH3(9-29) and Cc-CATH3(13-29) appeared to have lost activities. Cc-CATH3(1-29) and Cc-CATH3(5-29) possessed antibacterial activity with minimum inhibitory concentrations of 2–4 and 1–2 µM, respectively. For cytotoxicity, Cc-CATH3(1-29) and Cc-CATH3(5-29) displayed cytotoxicity with the IC50 values of 9.33 and 4.93 μM, respectively. Cc-CATH3(5-29) induced greater liposome membranes disruption than Cc-CATH3(1-29) regardless of lipid type and composition. The leakage results of Cc-CATH3(1-29) share a similar trend with that in Cc-CATH3(5-29); they exhibit no preferential binding to anionic phospholipids. In conclusion, the results suggested that the first four residues at the N-terminus “RVRR” is not essential for presenting all test activities. In contrast, residues five to eight of “FWPL” are necessary as the exclusion of this short motif in Cc-CATH3(9-29) and Cc-CATH3(13-29) leads to a loss of activities. This study will be beneficial for further design and development of Cc-CATH3 to be novel antibiotic.
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This project is supported by the Office of the High Education Commission and Mahidol University under the National Research Universities Initiative.
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Jittikoon, J., Ngamsaithong, N., Pimthon, J. et al. Effect of N-terminal truncation on antibacterial activity, cytotoxicity and membrane perturbation activity of Cc-CATH3. Arch. Pharm. Res. 38, 1839–1849 (2015). https://doi.org/10.1007/s12272-015-0600-0
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DOI: https://doi.org/10.1007/s12272-015-0600-0