Synthesis and Properties of a Heterodetic Cyclic Peptide: Gramicidin S Analog Containing Disulfide Bond

Satoh, Kenichi; Okuda, Hidenobu; Horimoto, Hideaki; Kodama, Hiroaki; Kondo, Michio

doi:10.1246/bcsj.63.3467

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Although these peptides commonly have antimicrobial activity against pathogens, there are many variations in their primary structures. For relationship between structure and activity, linearization of cyclic antimicrobial peptides generally alters their activities as well as their ability to interact with cell membranes28–33. Furthermore, Peng et al reported that the positive patch and the hydrophobic surface were both important for the antifungal function of Pa ‐AMP from poke weed ( P. americana ) seeds34.…”

Section: Discussionmentioning

confidence: 99%

The chitin‐binding capability of Cy‐AMP1 from cycad is essential to antifungal activity

Yokoyama

Iida

Kawasaki

et al. 2009

Journal of Peptide Science

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Antimicrobial peptides are important components of the host innate immune responses by exerting broad-spectrum microbicidal activity against pathogenic microbes. Cy-AMP1 found in the cycad (Cycas revoluta) seeds has chitin-binding ability, and the chitin-binding domain was conserved in knottin-type and hevein-type antimicrobial peptides. The recombinant Cy-AMP1 was expressed in Escherichia coli and purified to study the role of chitin-binding domain. The mutants of Cy-AMP1 lost chitin-binding ability completely, and its antifungal activity was markedly decreased in comparison with native Cy-AMP1. However, the antimicrobial activities of the mutant peptides are nearly identical to that of native one. It was suggested that the chitin-binding domain plays an essential role in antifungal, but not antimicrobial, activity of Cy-AMP1.

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Section: Discussionmentioning

confidence: 99%

The chitin‐binding capability of Cy‐AMP1 from cycad is essential to antifungal activity

Yokoyama

Iida

Kawasaki

et al. 2009

Journal of Peptide Science

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“…Linearization of cyclic antimicrobial peptides generally alters their activities as well as their ability to interact with membranes (9)(10)(11)(12)(13)31,38,39). Matsuzaki et al have shown that a linear analog of tachyplesin I, where all four SH groups of Cys residues are protected with acetamidomethy groups, exhibited more membrane disruption but much weaker membrane permeabilization activity than the parent peptide (11,13).…”

Section: Discussionmentioning

confidence: 99%

Deletion of All Cysteines in Tachyplesin I Abolishes Hemolytic Activity and Retains Antimicrobial Activity and Lipopolysaccharide Selective Binding

et al. 2006

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Tachyplesin I is a cyclic beta-sheet antimicrobial peptide isolated from the hemocytes of Tachypleus tridentatus. The four cysteine residues in tachyplesin I play a structural role in imparting amphipathicity to the peptide which has been shown to be essential for its activity. We investigated the role of amphipathicity using an analogue of tachyplesin I (TP-I), CDT (KWFRVYRGIYRRR-NH(2)), in which all four cysteines were deleted. Like TP-I, CDT shows antimicrobial activity and disrupts Escherichia coli outer membrane and model membranes mimicking bacterial inner membranes at micromolar concentrations. The CDT peptide does not cause hemolysis up to 200 microg/mL while TP-I showed about 10% hemolysis at 100 microg/mL and about 25% hemolysis at 150 microg/mL. Peptide-into-lipid titrations under isothermal conditions reveal that the interaction of CDT with lipid membranes is an enthalpy-driven process. Binding assays performed using fluorometry demonstrate that the peptide CDT binds and inserts into only negatively charged membranes. The peptide-induced thermotropic phase transition of MLVs formed of DMPC and the DMPC/DMPG (7:3) mixture suggests specific lipid-peptide interactions. The circular dichroism study shows that the peptide exists as an unordered structure in an aqueous buffer and adopts a more ordered beta-structure upon binding to negatively charged membrane. The NMR data suggest that CDT binding to negatively charged bilayers induces a change in the lipid headgroup conformation with the lipid headgroup moving out of the bilayer surface toward the water phase, and therefore, a barrel stave mechanism of membrane disruption is unlikely as the peptide is located near the headgroup region of lipids. The lamellar phase (31)P chemical shift spectra observed at various concentrations of the peptide in bilayers suggest that the peptide may function neither via fragmentation of bilayers nor by promoting nonlamellar structures. NMR and fluorescence data suggest that the presence of cholesterol inhibits the peptide binding to the bilayers. These properties help to explain that cysteine residues may not contribute to antimicrobial activity and that the loss of hemolytic activity is due to lack of hydrophobicity and amphipathicity.

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“…Acyclization of membrane-acting cyclic peptides generally reduces their potencies (Erlanger & Goode, 1954, 1959Makisumi et al, 1971a,b;Satoh et al, 1990;Tamamura et al, 1993a). However, the detailed mechanisms are still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Acyclization of gramicidin S •Abstract published in Advance ACS Abstracts, October 1, 1993. 1 Abbreviations: T-SS, tachyplesin I; T-Acm, an acyclic tachyplesin I analog with the four SH groups of tachyplesin I protected by acetamidomethyl groups; NMR, nuclear magnetic resonance; FTIR-PATR, Fourier transform infrared polarized attenuated total reflection; RP-HPLC, reversed-phase high-performance liquid chromatography; CD, circular dichroism; PC, egg yolk L-a-phosphatidylcholine; PG, L-aphosphatidylglycerol enzymatically converted from PC; LUVs, large unilamellar vesicles. ( Erlanger & Goode, 1954, 1959 and related peptides (Makisumi et al, 1971a,b;Satoh et al, 1990) significantly reduces their potencies. Thus, we synthesized a linear tachyplesin I derivative (T-Acm) in which the four SH groups of tachyplesin I were protected with Acm (acetamidomethyl) groups (Figure 1).…”

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confidence: 99%

Role of disulfide linkages in tachyplesin-lipid interactions

Nakayama¹,

Fukui²,

Otaka³

et al. 1993

Biochemistry

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In order to elucidate the role of the two disulfide linkages of tachyplesin I (T-SS), a membrane-acting cyclic antimicrobial peptide from Tachypleus tridentatus, we synthesized the acyclic analog (T-Acm) with the four SH groups protected by acetamidomethyl groups and also investigated the interactions of these peptides with lipid bilayers. T-SS induced leakage of calcein from egg yolk L-alpha-phosphatidylglycerol large unilamellar vesicles (PG LUVs) at peptide concentrations 1 order of magnitude smaller than those at which leakage was induced by T-Acm, which coincides with the stronger antimicrobial activities of T-SS. The micellization of PG LUVs was also more efficient for the cyclic peptide. Fluorescence titration studies revealed that binding affinities of both peptides to the PG membranes were similar. Fourier transform infrared polarized attenuated total reflection spectroscopy and fluorescence quenching experiments demonstrated that T-SS and T-Acm both form amphiphilic antiparallel beta-sheet structures in the membranes. They are formed in such a way that the sheet planes lie parallel to the membrane surface with the sheet hydrophobic surfaces penetrating slightly into the hydrophobic region of the bilayers. Furthermore, the observation that the linear T-Acm, the weaker membrane permeabilizer, caused a far more serious membrane disruption suggests the possibility that the mechanisms of membrane permeabilization by the cyclic peptide are different from those by the linear peptide, the latter being the disruption of the lipid organization.

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Synthesis and Properties of a Heterodetic Cyclic Peptide: Gramicidin S Analog Containing Disulfide Bond

Cited by 6 publications

References 11 publications

The chitin‐binding capability of Cy‐AMP1 from cycad is essential to antifungal activity

The chitin‐binding capability of Cy‐AMP1 from cycad is essential to antifungal activity

Deletion of All Cysteines in Tachyplesin I Abolishes Hemolytic Activity and Retains Antimicrobial Activity and Lipopolysaccharide Selective Binding

Role of disulfide linkages in tachyplesin-lipid interactions

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