title: Effect of N-terminal truncation on antibacterial activity, cytotoxicity and membrane perturbation activity of Cc-CATH3.
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.
authors: Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand. jiraphun.jit@mahidol.ac.th.|Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand. jiraphun.jit@mahidol.ac.th.
authors: Jiraphun
authors: J
authors: Jittikoon
authors: Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand.
authors: Narumon
authors: N
authors: Ngamsaithong
authors: Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand.|Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.
authors: Jutarat
authors: J
authors: Pimthon
authors: Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand.|Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.
authors: Opa
authors: O
authors: Vajragupta
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D054804:Cathelicidins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D008081:Liposomes; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D010743:Phospholipids / Q000378:metabolism; D011784:Quail
chemical_list: D000900:Anti-Bacterial Agents; D054804:Cathelicidins; D008081:Liposomes; D010743:Phospholipids
keywords: Antibacterial; Antimicrobial peptide; Cathelicidin; Cytotoxicity; Membrane perturbation; Peptide truncation