Effects of peptide dimerization on pore formation: Antiparallel disulfide-dimerized magainin 2 analogue

Hara, Toshiaki; Kodama, Hiroaki; Kondo, Michio; Wakamatsu, Kaori; Takeda, Akemi; Tachi, Tomoya; Matsuzaki, Katsumi

doi:10.1002/1097-0282(20010405)58:4<437::aid-bip1019>3.0.co;2-i

Cited by 63 publications

(34 citation statements)

References 38 publications

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“…Substituted residues are underlined. such as magainin 2 and melittin analogues showed stronger antimicrobial activity than the monomeric forms (18,19). Moreover, halocidin dimer congeners derived from halocidin, a dimeric α-helical structure peptide that was purified from the tunicate Halocynthia aurantium showed more potent antibacterial activity than the its monomer forms (20).…”

Section: Resultsmentioning

confidence: 99%

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Kim

Lee

Kwon

et al. 2013

International Journal of Oncology

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Abstract.Harmoniasin is a defensin-like antimicrobial peptide identified from the ladybug Harmonia axyridis. Among the synthetic homodimer peptide analogues derived from harmoniasin, HaA4 has been found to have antibacterial activity without hemolytic activity. In this study, we investigated whether HaA4 has anticancer activity against human leukemia cell lines such as U937 and Jurkat cells. HaA4 manifested cytotoxicity and decreased the cell viability of U937 and Jurkat cells in MTS assay and LDH release assay. We found that HaA4 induced apoptotic and necrotic cell death of the leukemia cells using flow cytometric analysis, acridine orange/ethidium bromide staining and nucleosomal fragmentation of genomic DNA. Activation of caspase-7 and -9 and fragmentation of poly (ADP-ribose) polymerase was detected in the HaA4-treated leukemia cells, suggesting induction of a caspase-dependent apoptosis pathway by HaA4. Caspase-dependent apoptosis was further confirmed by reversal of the HaA4-induced viability reduction by treatment of Z-VAD-FMK, a pan-caspase inhibitor. In conclusion, HaA4 caused necrosis and caspase-dependent apoptosis in both U937 and Jurkat leukemia cells, which suggests potential utility of HaA4 as a cancer therapeutic agent.

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Section: Resultsmentioning

confidence: 99%

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Kim

Lee

Kwon

et al. 2013

International Journal of Oncology

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“…Thus, the use of dimeric cAMPs remains controversial. To evaluate the effects of the length and polarity of the spacer used in the dimerization of Ctx-Ha, we synthesized the monomeric peptide and three different dimeric forms (Lys branched with different spacers) using SPPS methodology and determined their antimicrobial properties (11,16,23,39). The properties of the spacer could affect the interaction with the head groups of the membrane phospholipids or cell wall, which would change the biological activities of the peptides.…”

Section: Resultsmentioning

confidence: 99%

Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

Lorenzón

Cespedes

Vicente

et al. 2012

Antimicrob Agents Chemother

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It is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) and t-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

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“…Among the lactococcal bacteriocins, the sizes of the pores created by nisin and lacticin 3147 were 2 to 2.5 and 0.6 nm, respectively (33,34), while their antimicrobial activities were in the nanomolar range, as is the case for lacticin Q (4, 24). Although magainin 2 analogues, the magainin 2-peptidyl-glycylleucine-carboxyamide mixture, and melittin allow the leakage of FITC-dex with molecular weights of about 4,400 or lower, the peptide concentrations needed were higher than those needed for calcein leakage (12,19,21). The huge pore created by lacticin Q was also demonstrated on the bacterial membrane ( Fig.…”

Section: Discussionmentioning

confidence: 98%

Peptide-Lipid Huge Toroidal Pore, a New Antimicrobial Mechanism Mediated by a Lactococcal Bacteriocin, Lacticin Q

Yoneyama

Imura

Ohno

et al. 2009

Antimicrob Agents Chemother

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118

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Lacticin Q is a pore-forming bacteriocin produced by Lactococcus lactis QU 5, and its antimicrobial activity is in the nanomolar range. Lacticin Q induced calcein leakage from negatively charged liposomes. However, no morphological changes in the liposomes were observed by light scattering. Concomitantly with the calcein leakage, lacticin Q was found to translocate from the outer to the inner leaflet of the liposomes, after it initially bound to the membrane within 2 s. Lacticin Q also induced lipid flip-flop. These results reveal that the antimicrobial mechanism of lacticin Q can be described by the toroidal pore model. This is the first report of a bacteriocin of gram-positive bacteria that forms a toroidal pore. From liposomes, lacticin Q leaked fluorescence-labeled dextran with a diameter of 4.6 nm. In addition, lacticin Q caused the leakage of small proteins, such as the green fluorescent protein, from live bacterial cells. There are no other reports of antimicrobial peptides that exhibit protein leakage properties. The proposed pore formation model of lacticin Q is as follows: (i) quick binding to outer membrane leaflets; (ii) the formation of at least 4.6-nm pores, causing protein leakage with lipid flip-flop; and (iii) the migration of lacticin Q molecules from the outer to the inner membrane leaflets. Consequently, we termed the novel pore model in the antimicrobial mechanism of lacticin Q a "huge toroidal pore."

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Effects of peptide dimerization on pore formation: Antiparallel disulfide-dimerized magainin 2 analogue

Cited by 63 publications

References 38 publications

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Anticancer activity of a synthetic peptide derived from harmoniasin, an antibacterial peptide from the ladybug Harmonia axyridis

Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

Peptide-Lipid Huge Toroidal Pore, a New Antimicrobial Mechanism Mediated by a Lactococcal Bacteriocin, Lacticin Q

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