Oligomerization of protegrin‐1 in the presence of DPC micelles. A proton high‐resolution NMR study

Roumestand, Christian; Louis, V.; Aumelas, André; Grassy, G.; Calas, Bernard; Chavanieu, Alain

doi:10.1016/s0014-5793(97)01579-2

Cited by 95 publications

(100 citation statements)

References 24 publications

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“…Membrane pores formed by ␣-helical magainin as well as ␤-hairpin-shaped protegrin 1 produced a diffraction pattern similar to that of the well-established transmembrane gramicidin channel (8,10,39). Similar conclusions which relate the ability of cationic peptides to form aggregates to their antimicrobial potencies have recently been presented for dermaseptin S4 (4), protegrin 1 (26), and human defensins (29).…”

Section: Discussionsupporting

confidence: 70%

De Novo Design of Potent Antimicrobial Peptides

Frecer¹,

Ding³

2004

Antimicrob Agents Chemother

136

117

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Lipopolysaccharide (LPS), shed by gram-negative bacteria during infection and antimicrobial therapy, may lead to lethal endotoxic shock syndrome. A rational design strategy based on the presumed mechanism of antibacterial effect was adopted to design cationic antimicrobial peptides capable of binding to LPS through tandemly repeated sequences of alternating cationic and nonpolar residues. The peptides were designed to achieve enhanced antimicrobial potency due to initial bacterial membrane binding with a reduced risk of endotoxic shock. The peptides designed displayed binding affinities to LPS and lipid A (LA) in the low micromolar range and by molecular modeling were predicted to form amphipathic ␤-hairpin-like structures when they bind to LPS or LA. They also exhibited strong effects against gram-negative bacteria, with MICs in the nanomolar range, and low cytotoxic and hemolytic activities at concentrations significantly exceeding their MICs. Quantitative structure-activity relationship (QSAR) analysis of peptide sequences and their antimicrobial, cytotoxic, and hemolytic activities revealed that site-directed substitutions of residues in the hydrophobic face of the amphipathic peptides with less lipophilic residues selectively decrease the hemolytic effect without significantly affecting the antimicrobial or cytotoxic activity. On the other hand, the antimicrobial effect can be enhanced by substitutions in the polar face with more polar residues, which increase the amphipathicity of the peptide. On the basis of the QSARs, new analogs that have strong antimicrobial effects but that lack hemolytic activity can be proposed. The findings highlight the importance of peptide amphipathicity and allow a rational method that can be used to dissociate the antimicrobial and hemolytic effects of cationic peptides, which have potent antimicrobial properties, to be proposed.

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Section: Discussionsupporting

confidence: 70%

De Novo Design of Potent Antimicrobial Peptides

Frecer¹,

Ding³

2004

Antimicrob Agents Chemother

136

117

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“…7). Structurally, -defensins resemble tachyplesins (34) and protegrins (35)(36)(37). Tachyplesins such as T22 bind CXCR4 with high affinity and protect against HIV-1 strains that enter via this coreceptor (38).…”

Section: Discussionmentioning

confidence: 99%

Retrocyclin, an Antiretroviral θ-Defensin, Is a Lectin

Wang¹,

Cole²,

Hong³

et al. 2003

The Journal of Immunology

184

164

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θ-Defensins are circular octadecapeptides that contain an internal tridisulfide ladder. Because retrocyclin-1, an ancestral hominid θ-defensin, can protect human cells in vitro from infection by T- and M-tropic strains of HIV-1, we used surface plasmon resonance techniques to study its binding to glycoproteins and glycolipids implicated in HIV-1 entry. Retrocyclin-1 bound with high affinity to gp120 (Kd, 35.4 nM), CD4 (Kd, 31 nM), and galactosylceramide (Kd, 24.1 nM). Neither a circular form of retrocyclin without its tridisulfide ladder nor its β-hairpin precursor with these disulfides intact bound gp120 or CD4 effectively. Retrocyclin also bound fetuin, an extensively glycosylated protein, with high affinity, but it did not bind nonglycosylated gp120 or BSA. However, retrocyclin did bind to a neoglycoprotein, BSA, with covalently attached sugar residues. Experiments with glycosidase-treated fetuin, gp120, and CD4 revealed that both O-linked and N-linked sugars were used as binding sites. In a panel of retrocyclin variants, binding to immobilized gp120 and CD4 were highly correlated to each other and to the peptide’s ability to protect human PBMCs from infection by HIV-1. Although small, cysteine-rich antimicrobial peptides with lectin-like properties exist in plants, θ-defensins are the first such molecules to be identified in vertebrates. Retrocyclin’s ability to recognize and bind carbohydrate-containing surface molecules is integrally related to its ability to protect cells from HIV-1 infection.

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“…Animal protegrins consist of five cysteine-rich naturally occurring cationic antimicrobial peptides [96]. In porcine leukocytes, protegrins contain 16 residues with four cysteines stabilized by two intramolecular disulphide bonds [97].…”

Section: Cysteine-stabilized Peptides With a B-sheet Structurementioning

confidence: 99%

“…Although the primary amino acid sequences of the protegrins show minimal homology to the b-defensins, the first 3-cysteine residues are spaced identically to those of a-defensins [97]. Two antiparallel b-sheets are linked by a b-hairpin turn [96]. In artificial membranes, they form dimeric structures, which aggregate forming a larger pore [96].…”

Section: Cysteine-stabilized Peptides With a B-sheet Structurementioning

confidence: 99%

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Antimicrobial peptides in animals and their role in host defences

Brogden

Ackermann

McCray

et al. 2003

International Journal of Antimicrobial Agents

415

287

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Domesticated animals have a large variety of antimicrobial peptides that serve as natural innate barriers limiting microbial infection or, in some instances, act as an integral component in response to inflammation or microbial infection. These peptides differ in size, composition, mechanisms of activity and range of antimicrobial specificities. They are expressed in many tissues, polymorphonuclear leukocytes, macrophages and mucosal epithelial cells. There is a small group of anionic antimicrobial peptides found in ruminants and a much larger group of cationic antimicrobial peptides found in all domesticated animals. The cationic peptides include linear, helical peptides, linear peptides rich in proline and cysteine-stabilized peptides with a b-sheet and are commonly referred to as cathelicidins and defensins. These peptides are generally broad-spectrum for Gram-positive bacteria, Gram-negative bacteria and fungi (e.g. myeloid antimicrobial peptides, a-, bdefensins, and protegrins) or are specific to one of these groups (e.g. porcine cecropin P1, Bac5, Bac7, PR-39 and prophenin). RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. Abstract Domesticated animals have a large variety of antimicrobial peptides that serve as natural innate barriers limiting microbial infection or, in some instances, act as an integral component in response to inflammation or microbial infection. These peptides differ in size, composition, mechanisms of activity and range of antimicrobial specificities. They are expressed in many tissues, polymorphonuclear leukocytes, macrophages and mucosal epithelial cells. There is a small group of anionic antimicrobial peptides found in ruminants and a much larger group of cationic antimicrobial peptides found in all domesticated animals. The cationic peptides include linear, helical peptides, linear peptides rich in proline and cysteine-stabilized peptides with a b-sheet and are commonly referred to as cathelicidins and defensins. These peptides are generally broad-spectrum for Gram-positive bacteria, Gram-negative bacteria and fungi (e.g. myeloid antimicrobial peptides, a-, b-defensins, and protegrins) or are specific to one of these groups (e.g. porcine cecropin P1, Bac5, Bac7, PR-39 and prophenin). Published by Elsevier B.V.

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Oligomerization of protegrin‐1 in the presence of DPC micelles. A proton high‐resolution NMR study

Cited by 95 publications

References 24 publications

De Novo Design of Potent Antimicrobial Peptides

De Novo Design of Potent Antimicrobial Peptides

Retrocyclin, an Antiretroviral θ-Defensin, Is a Lectin

Antimicrobial peptides in animals and their role in host defences

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