|
KMID : 0043320150380101839
|
|
Archives of Pharmacal Research
2015 Volume.38 No. 10 p.1839 ~ p.1849
|
|
|
Effect of N-terminal truncation on antibacterial activity, cytotoxicity and membrane perturbation activity of Cc-CATH3
|
|
Jittikoon Jiraphun
Ngamsaithong Narumon
Pimthon Jutarat
Vajragupta Opa
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Antimicrobial peptide, Cathelicidin, Peptide truncation, Antibacterial, Cytotoxicity, Membrane perturbation
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|