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Molecules
2021 Jan 16;262:. doi: 10.3390/molecules26020444.
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Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence.
Hirano M
,
Saito C
,
Yokoo H
,
Goto C
,
Kawano R
,
Misawa T
,
Demizu Y
.
???displayArticle.abstract??? Magainin 2 (Mag2), which was isolated from the skin of the African clawed frog, is a representative antimicrobial peptide (AMP) that exerts antimicrobial activity via microbial membrane disruption. It has been reported that the helicity and amphipathicity of Mag2 play important roles in its antimicrobial activity. We investigated and recently reported that 17 amino acid residues of Mag2 are required for its antimicrobial activity, and accordingly developed antimicrobial foldamers containing α,α-disubstituted amino acid residues. In this study, we further designed and synthesized a set of Mag2 derivatives bearing the hydrocarbon stapling side chain for helix stabilization. The preferred secondary structures, antimicrobial activities, and cell-membrane disruption activities of the synthesized peptides were evaluated. Our analyses revealed that hydrocarbon stapling strongly stabilized the helical structure of the peptides and enhanced their antimicrobial activity. Moreover, peptide 2 stapling between the first and fifth position from the N-terminus showed higher antimicrobial activity than that of Mag2 against both gram-positive and gram-negative bacteria without exerting significant hemolytic activity. To investigate the modes of action of tested peptides 2 and 8 in antimicrobial and hemolytic activity, electrophysiological measurements were performed.
20mk0101120j0003 Japan Agency for Medical Research and Development, 20k22711, H.Y.; 18k14880, T.M.; 17k08385 and 18H05502, Y.D. Japan Society for the Promotion of Science , Y.D. TERUMO FOUNDATION for Life Sciences and ARTS, Y.D. Takeda Science foundation, Y.D. the Naito Foundation, Y.D. the Sumitomo Foundation, Y.D. the Kobayashi Foundation for Cancer Research, Y.D. the NOVARTIS Foundation (Japan) for the Promotion of Science
Figure 1. The peptide design based on the essential fragment of magainin 2 (Mag2).
Figure 3. (a) Electrophysiological measurement [18]. (b) Typical current patterns with the treatment of cell penetrating peptides (CPPs) and antimicrobial peptides (AMPs) [18]. (c) The electrophysiological signals during treatment of peptides 1, 2, and 8 at 100 nM.
Figure 4. Scores for peptides 1, 2, and 8 used for the pore-formation activity analysis. The total score of pore formation, charge flux, pore diameter, and pore stability against (a) 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)/1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG) and (b) 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane was evaluated for peptides 1, 2, and 8.
Akishiba,
Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide.
2017, Pubmed
Akishiba,
Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide.
2017,
Pubmed
Ali,
Stapled Peptides Inhibitors: A New Window for Target Drug Discovery.
2019,
Pubmed
Chang,
Origin and proliferation of multiple-drug resistance in bacterial pathogens.
2015,
Pubmed
Goto,
Development of Amphipathic Antimicrobial Peptide Foldamers Based on Magainin 2 Sequence.
2019,
Pubmed
,
Xenbase
Kawano,
Automated parallel recordings of topologically identified single ion channels.
2013,
Pubmed
Kim,
Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii.
2018,
Pubmed
,
Xenbase
Krishnakumari,
N-Terminal fatty acylation of peptides spanning the cationic C-terminal segment of bovine β-defensin-2 results in salt-resistant antibacterial activity.
2015,
Pubmed
Li,
Novel Stapling by Lysine Tethering Provides Stable and Low Hemolytic Cationic Antimicrobial Peptides.
2020,
Pubmed
Li,
Helical Antimicrobial Sulfono-γ-AApeptides.
2015,
Pubmed
Lin,
Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.
2015,
Pubmed
Misawa,
Rational design of novel amphipathic antimicrobial peptides focused on the distribution of cationic amino acid residues.
2019,
Pubmed
Mourtada,
Design of stapled antimicrobial peptides that are stable, nontoxic and kill antibiotic-resistant bacteria in mice.
2019,
Pubmed
Nikaido,
Multidrug resistance in bacteria.
2009,
Pubmed
Porter,
Non-haemolytic beta-amino-acid oligomers.
2000,
Pubmed
Saigo,
Electrophysiological Analysis of Antimicrobial Peptides in Diverse Species.
2019,
Pubmed
Sekiya,
Electrophysiological Analysis of Membrane Disruption by Bombinin and Its Isomer Using the Lipid Bilayer System.
2019,
Pubmed
Sekiya,
Channel current analysis estimates the pore-formation and the penetration of transmembrane peptides.
2018,
Pubmed
,
Xenbase
Strandberg,
Influence of hydrophobic residues on the activity of the antimicrobial peptide magainin 2 and its synergy with PGLa.
2015,
Pubmed
,
Xenbase
Walensky,
Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix.
2004,
Pubmed
Yamashita,
Development of a Cell-penetrating Peptide that Exhibits Responsive Changes in its Secondary Structure in the Cellular Environment.
2016,
Pubmed
Yokoo,
De Novo Design of Cell-Penetrating Foldamers.
2020,
Pubmed
Zweytick,
Influence of N-acylation of a peptide derived from human lactoferricin on membrane selectivity.
2006,
Pubmed