title: Effects and mechanisms of the secondary structure on the antimicrobial activity and specificity of antimicrobial peptides.
abstract: A 15-mer cationic α-helical antimicrobial peptide HPRP-A1 was used as the parent peptide to study the effects of peptide secondary structure on the biophysical properties and biological activities. Without changing the amino acid composition of HPRP-A1, we designed two α-helical peptides with either higher or lower helicity compared with the parent peptide, a β-sheet peptide and a random coiled peptide using de novo design approach. The secondary structures were confirmed by circular dichroism spectroscopy. The three α-helical peptides exhibited comparable antibacterial activities, but their hemolytic activity varied from extreme hemolysis to no hemolysis, which is correlated with their helicity. The β-sheet peptide shows poor antibacterial and strong hemolytic activities. More interestingly, the random coil peptide shows no antibacterial activity against Gram-negative bacteria, weak antibacterial activity against Gram-positive bacteria, and extremely weak hemolytic activity. Bacterial membrane permeabilization was also testified on peptides with different secondary structures. Tryptophan fluorescence experiment revealed that the peptide binding preference to the lipid vesicles for mimicking the prokaryotic or eukaryotic membranes was consistent with their biological activities. With the de novo design approach, we proved that it is important to maintain certain contents of amphipathic secondary structure for a desirable biological activity. We believe that the de novo design approach of relocation of the amino acids within a template sequence could be an effective approach in optimizing the specificity of an antimicrobial peptide.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, Jilin, 130012, China.|School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Xuan-thanh
authors.initials: XT
authors.lastname: Mai
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin, 130024, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, Jilin, 130012, China.|School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Tan
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, Jilin, 130012, China.|School of Life Sciences, Jilin University, Changchun, 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, Jilin, 130012, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, Jilin, 130012, China.|School of Life Sciences, Jilin University, Changchun, 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, Jilin, 130012, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000254:growth & development; D015195:Drug Design; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013210:Staphylococcus / Q000187:drug effects / Q000254:growth & development; D055672:Static Electricity; D013329:Structure-Activity Relationship; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D053835:Unilamellar Liposomes
keywords: antimicrobial peptide; mechanism of action; secondary structure; specificity