Generation of novel cationic antimicrobial peptides from natural non-antimicrobial sequences by acid-amide substitution

Annals of Clinical Microbiology and Antimicrobials

Research

Satoshi Ueno¹  Toshimasa Yamazaki¹  Yusuke Kato¹  Yasushi Tamada¹  Masaomi Minaba¹  Misako Taichi²  Yuji Nishiuchi² 

[1] National Institute of Agrobiological Sciences, Oowashi 1-2, 305-8634, Tsukuba, Ibaraki, Japan;SAITO Research Center, Peptide Institute, Inc.,, 567-0085, Osaka, Ibaraki, Japan;

关键词: Circular Dichroism Spectrum;    Liposome Membrane;    Parent Sequence;    Cationic Antimicrobial Peptide;    Bacterial Killing Activity;   

DOI  :  10.1186/1476-0711-10-11

 received in 2010-09-07, accepted in 2011-03-22,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundCationic antimicrobial peptides (CAMPs) are well recognized to be promising as novel antimicrobial and antitumor agents. To obtain novel skeletons of CAMPs, we propose a simple strategy using acid-amide substitution (i.e. Glu→Gln, Asp→Asn) to confer net positive charge to natural non-antimicrobial sequences that have structures distinct from known CAMPs. The potential of this strategy was verified by a trial study.MethodsThe pro-regions of nematode cecropin P1-P3 (P1P-P3P) were selected as parent sequences. P1P-P3P and their acid-amide-substituted mutants (NP1P-NP3P) were chemically synthesized. Bactericidal and membrane-disruptive activities of these peptides were evaluated. Conformational changes were estimated from far-ultraviolet circular dichroism (CD) spectra.ResultsNP1P-NP3P acquired potent bactericidal activities via membrane-disruption although P1P-P3P were not antimicrobial. Far-ultraviolet CD spectra of NP1P-NP3P were similar to those of their parent peptides P1P-P3P, suggesting that NP1P-NP3P acquire microbicidal activity without remarkable conformational changes. NP1P-NP3P killed bacteria in almost parallel fashion with their membrane-disruptive activities, suggesting that the mode of action of those peptides was membrane-disruption. Interestingly, membrane-disruptive activity of NP1P-NP3P were highly diversified against acidic liposomes, indicating that the acid-amide-substituted nematode cecropin pro-region was expected to be a unique and promising skeleton for novel synthetic CAMPs with diversified membrane-discriminative properties.ConclusionsThe acid-amide substitution successfully generated some novel CAMPs in our trial study. These novel CAMPs were derived from natural non-antimicrobial sequences, and their sequences were completely distinct from any categories of known CAMPs, suggesting that such mutated natural sequences could be a promising source of novel skeletons of CAMPs.

【 授权许可】

Unknown   
© Ueno et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.