Intramolecular Disulfide Bonds Enhance the Antimicrobial and Lytic Activities of Protegrins at Physiological Sodium Chloride Concentrations

Harwig, Sylvia S.L.; Waring, Alan J.; Yang, Hye Jin; Cho, Yoon; Tan, Leonie; Lehrer, Robert I.

doi:10.1111/j.1432-1033.1996.0352h.x

Cited by 138 publications

(169 citation statements)

References 41 publications

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“…Intramolecular disulfide bridges for maintaining the antiparallel β-sheet structure are believed to be required for the peptides to form pores in the membrane, as demonstrated in Xenopus laevis oocytes [76]. In fact, the antimicrobial activity of a linearized protegrin variant is decreased remarkably [52]. The minimal structure of protegrin-1 for activity against N. gonorrhoeae and C. trachomatis is defined within the central region of the molecule (residues 5-16), and optimal activity requires both intramolecular disulfide bridges [52,76,92,128].…”

Section: Protegrins a Group Of Compactmentioning

confidence: 93%

“…In contrast to defensins, antimicrobial activities of protegrins are maintained at physiological NaCl concentrations and are not inhibited by extracellular cations or serum components [52]. Intramolecular disulfide bridges for maintaining the antiparallel β-sheet structure are believed to be required for the peptides to form pores in the membrane, as demonstrated in Xenopus laevis oocytes [76].…”

Section: Protegrins a Group Of Compactmentioning

confidence: 99%

“…In fact, the antimicrobial activity of a linearized protegrin variant is decreased remarkably [52]. The minimal structure of protegrin-1 for activity against N. gonorrhoeae and C. trachomatis is defined within the central region of the molecule (residues 5-16), and optimal activity requires both intramolecular disulfide bridges [52,76,92,128]. The small size, stability, and overall effectiveness, combined with a substantial lack of cytotoxicity to host cells, make protegrins promising topical therapeutics to prevent and treat human sexually transmitted diseases and periodontal infections.…”

Section: Protegrins a Group Of Compactmentioning

confidence: 99%

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Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Zhang¹,

Ross²,

Blecha³

2000

Vet. Res.

106

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-Antimicrobial peptides (AMPs) are small, endogenous, polycationic molecules that constitute a ubiquitous and significant component of innate immunity. These natural antibiotics have broad microbicidal activity against various bacteria, fungi, and enveloped viruses. Because most AMPs kill bacteria by physical disruption of cell membranes, which may prevent microorganisms from developing resistance against these agents, they are being explored as possible alternatives to conventional antibiotics. Pigs, like many other mammals, produce an impressive array of AMPs, which are synthesized predominantly by host leukocytic phagocytes or mucosal epithelial cells. Currently, more than a dozen distinct porcine AMPs have been identified and a majority belongs to the cathelicidin family. This review briefly summarizes recent advances in porcine AMP research with an emphasis on the diverse biological functions of each peptide. Mechanisms of action of these AMPs and their role in the resistance to infections are considered. Finally, the current status of pharmaceutical and agricultural uses of AMPs as well as future prospects for their application in the food animal industry is discussed.pig / antimicrobial peptide / cathelicidin / defensin / innate immunity Résumé -Peptides antimicrobiens porcins : nouvelles perspectives pour d'anciennes molécules de défense de l'hôte. Les peptides antimicrobiens sont de petites molécules endogènes, polycationiques, qui représentent un élément important et ubiquitaire des défenses immunes naturelles. Ces antibiotiques naturels ont un effet antimicrobien à large spectre, à la fois contre des bactéries, des moisissures et des virus enveloppés. Comme la plupart de ces peptides antimicrobiens tuent les bactéries par altération physique de leur membrane, ce qui peut éviter le développement de souches microbiennes résistantes à ces agents, ils représentent des alternatives possibles à l'emploi des antibiotiques classiques. Le porc, comme de nombreux autres mammifères, produit une gamme importante de peptides antimicrobiens, synthétisés pour l'essentiel par les leucocytes à activité phagocytaire, ou par les cellules épithéliales des muqueuses. Il y a actuellement plus d'une douzaine de peptides antimicrobiens identifiés chez le porc, dont la majorité fait partie de la famille des cathélicidines. Cet article résume les progrès récents accomplis dans le domaine des peptides antimicrobiens du porc, Vet. Res. 31 (2000) 277-296 277

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Section: Protegrins a Group Of Compactmentioning

confidence: 93%

Section: Protegrins a Group Of Compactmentioning

confidence: 99%

Section: Protegrins a Group Of Compactmentioning

confidence: 99%

See 1 more Smart Citation

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Zhang¹,

Ross²,

Blecha³

2000

Vet. Res.

106

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“…5). Antimicrobial peptides with similar spectra include tachyplesins (22), protegrins (11), and circularized defensins (23). Fig.…”

Section: Resultsmentioning

confidence: 99%

Retrocyclin: A primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1

Cole

Hong

Boo

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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270

319

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Human bone marrow expresses a pseudogene that encodes an antimicrobial peptide homologous to rhesus monkey circular minidefensins ( -defensins). We prepared the putative ancestral human peptide by solid-phase synthesis and named it ''retrocyclin.'' Retrocyclin did not cause direct inactivation of HIV-1, and its modest antibacterial properties resembled those of its rhesus homologs. Nevertheless, retrocyclin had a remarkable ability to inhibit proviral DNA formation and to protect immortalized and primary human CD4 ؉ lymphocytes from in vitro infection by both T-tropic and M-tropic strains of HIV-1. Confocal fluorescent microscopy studies performed with BODIPY-FL-labeled RC-101, a close analog of retrocyclin, showed that the peptide formed patch-like aggregates on the surface of CD4 ؉ cells. These findings suggest that retrocyclin interferes with an early stage of HIV-1 infection and that retrocyclin-like agents might be useful topical agents to prevent sexually acquired HIV-1 infections.

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“…In vitro, PG-1 is known to be toxic for many bacteria including E. coli (22), Listeria monocytogenes (22,27), and Neisseria gonorrhoeae (28,29). It also kills the fungus Candida albicans (22,30) and can protect cells from in vitro HIV infection (31).…”

mentioning

confidence: 99%

Interaction of antimicrobial peptide protegrin with biomembranes

Gidalevitz

Ishitsuka

Muresan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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209

174

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The antimicrobial peptide protegrin-1 (PG-1) interacts with membranes in a manner that strongly depends on membrane lipid composition. In this research we use an approach representing the outer layers of bacterial and red blood cell membranes with lipid monolayers and using a combination of insertion assay, epifluorescence microscopy, and surface x-ray scattering to gain a better understanding of antimicrobial peptide's mechanism of action. We find that PG-1 inserts readily into anionic dipalmitoyl-phosphatidylglycerol, palmitoyl-oleoyl-phosphatidylglycerol, and lipid A films, but significantly less so into zwitterionic dipalmitoyl-phosphatidylcholine, palmitoyl-oleoyl-phosphatidylcholine, and dipalmitoyl-phosphatidylethanolamine monolayers under similar experimental conditions. Epifluorescence microscopy shows that the insertion of PG-1 into the lipid layer results in the disordering of lipid packing; this disordering effect is corroborated by grazing incidence x-ray diffraction data. X-ray reflectivity measurements further point to the location of the peptide in the lipid matrix. In a pathologically relevant example we show that PG-1 completely destabilizes monolayer composed of lipid A, the major component in the outer membrane of Gram-negative bacteria, which is likely to be the mechanism by which PG-1 disrupts the outer membrane, thus allowing it to reach the target inner membrane.

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Intramolecular Disulfide Bonds Enhance the Antimicrobial and Lytic Activities of Protegrins at Physiological Sodium Chloride Concentrations

Cited by 138 publications

References 41 publications

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Retrocyclin: A primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1

Interaction of antimicrobial peptide protegrin with biomembranes

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