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A Comparative Study On The Structure And Function Of A Cytolytic α‐helical Peptide And Its Antimicrobial β‐sheet Diastereomer
Z. Oren, J. Hong, Y. Shai
Published 1999 · Chemistry
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Antimicrobial peptides which adopt mainly or only β-sheet structures have two or more disulfide bonds stabilizing their structure. The disruption of the disulfide bonds results in most cases in a large decrease in their antimicrobial activity. In the present study we examined the effect of d-amino acids incorporation on the structure and function of a cytolytic α-helical peptide which acts on erythrocytes and bacteria. The influence of a single or double d-amino acid replacement in α-helical peptides on their structure was reported previously in 50% 2,2,2,trifluoroethanol/water [Krause et al. (1995) Anal. Chem.67, 252–258]. Here we used Attenuated Total Reflectance Fourier-Transform Infrared (ATR-FTIR) spectroscopy and found that the predominant structure of the wild-type peptide is α-helix in phospholipid membranes, whereas the structure of the diastereomer is β-sheet. However, the linear, β-sheet diastereomer preserved its cytolytic activity on bacteria but not on erythrocytes. Previous studies have shown that the ability of antimicrobial peptides to lyse bacteria but not normal mammalian cells correlated with their ability to disintegrate preferentially negatively charged, but not zwitterionic phospholipid membranes. In contrast, the diastereomer described here disrupts zwitterionic and negatively charged vesicles with similar potencies to those of the hemolytic wild-type peptide. Interestingly, whereas addition of a positive charge to the N-terminus of the wild-type peptide (which caused a minor effect on its structure) increased activity only towards some of the bacteria tested, similar modification in the diastereomer increased activity towards all of them. Furthermore, the modified wild-type peptide preserved its potency to destabilize zwitterionic and negatively charged vesicles, whereas the modified diastereomer had a reduced potency on zwitterionic vesicles but increased potency on negatively charged vesicles. Overall our results suggest that this new class of antimicrobial diastereomeric peptides bind to the membrane in ‘carpet-like’ manner followed by membrane disruption and breakdown, rather than forming a transmembrane pore which interfere with the bacteria potential. These studies also open a way to design new broad-spectrum antibacterial peptides.
This paper references
The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders*
M. Frohm (1997)
The gel phase of dipalmitoyl phosphatidylcholine. An infrared characterization of the acyl chain packing.
D. Cameron (1980)
The use and misuse of FTIR spectroscopy in the determination of protein structure.
M. Jackson (1995)
Diffusion potential cascade. Convenient detection of transferable membrane pores.
L. Loew (1983)
Mode of action of the antibacterial cecropin B2: a spectrofluorometric study.
E. Gazit (1994)
Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles.
E. Gazit (1995)
Design and synthesis of amphiphilic alpha-helical model peptides with systematically varied hydrophobic-hydrophilic balance and their interaction with lipid- and bio-membranes.
T. Kiyota (1996)
Augmentation of the antibacterial activity of magainin by positive-charge chain extension.
R. Bessalle (1992)
The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.
G. Gudmundsson (1996)
Sequence and specificity of two antibacterial proteins involved in insect immunity
H. Steiner (1981)
Purification, primary structures, and antibacterial activities of β-defensins, a new family of antimicrobial peptides from bovine neutrophils.
M. Selsted (1996)
Peptide antibiotics and their role in innate immunity.
H. G. Boman (1995)
Orientation of fusion-active synthetic peptides in phospholipid bilayers: determination by Fourier transform infrared spectroscopy.
R. Ishiguro (1993)
Polarized attenuated total reflectance spectra of oriented purple membranes.
P. W. Yang (1987)
Diastereomers of Cytolysins, a Novel Class of Potent Antibacterial Peptides (*)
Y. Shai (1996)
Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin.
A. Mor (1991)
The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy.
A. Verkleij (1973)
Analysis of membrane and surface protein sequences with the hydrophobic moment plot.
D. Eisenberg (1984)
N-terminal analogues of cecropin A: synthesis, antibacterial activity, and conformational properties.
D. Andreu (1985)
Cell-lytic and antibacterial peptides that act by perturbing the barrier function of membranes: facets of their conformational features, structure-function correlations and membrane-perturbing abilities.
G. Saberwal (1994)
Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes.
Y. Pouny (1992)
Isolation and structure of novel defensive peptides from frog skin.
A. Mor (1994)
Molecular recognition between membrane-spanning polypeptides.
Y. Shai (1995)
Internal reflection spectroscopy
N. Harrick (1967)
Structure effects of double D-amino acid replacements: a nuclear magnetic resonance and circular dichroism study using amphipathic model helices.
S. Rothemund (1995)
Channel formation properties of synthetic pardaxin and analogues.
Y. Shai (1990)
Lipid composition as a guide to the classification of bacteria.
N. Shaw (1974)
NK‐lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity.
M. Andersson (1995)
Selective lysis of bacteria but not mammalian cells by diastereomers of melittin: structure-function study.
Z. Oren (1997)
Studies on the mechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesicles.
P. Sims (1974)
NK-lysin, a Disulfide-containing Effector Peptide of T-lymphocytes, Is Reduced and Inactivated by Human Thioredoxin Reductase
M. Andersson (1996)
Change of glutamic acid to lysine in a 13-residue antibacterial and hemolytic peptide results in enhanced antibacterial activity without increase in hemolytic activity.
N. Sitaram (1992)
Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins
V. Kokryakov (1993)
Anomalous amide I infrared absorption of purple membrane.
K. Rothschild (1979)
Hemolytic and antimicrobial activities of the twenty-four individual omission analogues of melittin.
S. Blondelle (1991)
Physicochemical determinants for the interactions of magainins 1 and 2 with acidic lipid bilayers.
K. Matsuzaki (1991)
Sequencing and synthesis of pardaxin, a polypeptide from the Red Sea Moses sole with ionophore activity
Y. Shai (1988)
Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes.
E. Gazit (1996)
Amphipathic helix motif: Classes and properties
J. Segrest (1990)
A synthetic all D-amino acid peptide corresponding to the N-terminal sequence of HIV-1 gp41 recognizes the wild-type fusion peptide in the membrane and inhibits HIV-1 envelope glycoprotein-mediated cell fusion.
M. Pritsker (1998)
Insect defensins: inducible antibacterial peptides.
J. Hoffmann (1992)
Synthetic magainin analogues with improved antimicrobial activity
H. Chen (1988)
The chemical synthesis of cecropin D and an analog with enhanced antibacterial activity.
J. Fink (1989)
Antimicrobial activity and conformation of tachyplesin I and its analogs.
H. Tamamura (1993)
A class of highly potent antibacterial peptides derived from pardaxin, a pore-forming peptide isolated from Moses sole fish Pardachirus marmoratus.
Z. Oren (1996)
Purification and pore-forming activity of two hydrophobic polypeptides from the secretion of the Red Sea Moses sole (Pardachirus marmoratus).
P. Lazarovici (1986)
Conformational and functional study of magainin 2 in model membrane environments using the new approach of systematic double-D-amino acid replacement.
T. Wieprecht (1996)
Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). Isolation and chemical structure.
T. Nakamura (1988)
Location of an amphipathic alpha-helix in peptides using reversed-phase HPLC retention behavior of D-amino acid analogs.
E. Krause (1995)
The Amphipathic Helix
R. Epand (1993)
Synthesis of the antibacterial peptide cecropin A (1-33).
R. Merrifield (1982)
Defensins: antimicrobial and cytotoxic peptides of mammalian cells.
R. Lehrer (1993)
Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor
M. Zasloff (1987)
Peptides as weapons against microorganisms in the chemical defense system of vertebrates.
P. Nicolas (1995)
Protegrin structure and activity against Neisseria gonorrhoeae.
X. D. Qu (1997)
Effects on electrophoretic mobility and antibacterial spectrum of removal of two residues from synthetic sarcotoxin IA and addition of the same residues to cecropin B
Z. Li (1988)
Solution structure of pardaxin P-2.
M. Zagorski (1991)
This paper is referenced by
Biological activities of retro and diastereo analogs of a 13-residue peptide with antimicrobial and hemolytic activities.
C. Subbalakshmi (2001)
Antimicrobial peptides: Their physicochemical properties and therapeutic application
S. Kang (2012)
Congeners of SMAP29 Kill Ovine Pathogens and Induce Ultrastructural Damage in Bacterial Cells
V. C. Kalfa (2001)
Interaction of the Gelsolin-Derived Antibacterial PBP 10 Peptide with Lipid Bilayers and Cell Membranes
R. Bucki (2006)
Design, Synthesis and Characterization of Cationic Peptide and Steroid Antibiotics
P. Savage (2002)
Peptide interaction with and insertion into membranes.
Ron Saar Dover (2013)
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Shasha Jiang (2019)
Mechanistic and Functional Studies of the Interaction of a Proline-rich Antimicrobial Peptide with Mammalian Cells*
L. Tomasinsig (2006)
The Consequence of Sequence Alteration of an Amphipathic α-Helical Antimicrobial Peptide and Its Diastereomers*
N. Papo (2002)
Antimicrobial and Antitumor Activities of Novel Peptides Derived from the Lipopolysaccharide- and β-1,3-Glucan Binding Protein of the Pacific Abalone Haliotis discus hannai
B. Nam (2016)
In vitro activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates.
U. Pag (2004)
Ideally amphipathic β-sheeted peptides at interfaces: structure, orientation, affinities for lipids and hemolytic activity of (KL)mK peptides
S. Castano (2000)
Chapter 7 Review Mechanism and Design of Microbicidal Peptides
J. Krijgsveld (2012)
Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci
Vera Sass (2010)
Isolation and characterisation of crocosin, an antibacterial compound from crocodile (Crocodylus siamensis) plasma.
Sutthidech Preecharram (2010)
Structure–Activity Study, Characterization, and Mechanism of Action of an Antimicrobial Peptoid D2 and Its d- and l-Peptide Analogues
Ines Greco (2019)
Fractionnement d'un hydrolysat peptidique de co-produits de crabe des neiges par électrodialyse avec membranes d'ultrafiltration : impact des paramètres liés au procédé sur la migration et la sélectivité peptidique
A. Doyen (2011)
Antibacterial activity of plasma from crocodile (Crocodylus siamensis) against pathogenic bacteria
Jintana Kommanee (2012)
PÉPTIDOS ANTIMICROBIANOS: ESTRUCTURA, FUNCIÓN Y APLICACIONES ANTIMICROBIAL PEPTIDES: STRUCTURE, FUNCTION AND APPLICATIONS
P. Gutiérrez (2003)
Activity Determinants of Helical Antimicrobial Peptides: A Large-Scale Computational Study
Y. He (2013)
Diversity of antimicrobial peptides and their mechanisms of action.
R. Epand (1999)
Graphical Techniques to Visualize the Amphiphilic Structures of Antimicrobial Peptides
D. Phoenix (2013)
From “carpet” mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides
Y. Shai (2001)
Mode of action of membrane active antimicrobial peptides.
Y. Shai (2002)
Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes?
N. Papo (2003)
Pleurocidin congeners demonstrate activity against Streptococcus and low toxicity on gingival fibroblasts.
M. Zhang (2016)
Effects of the antimicrobial peptide PGLa on live Escherichia coli.
A. da Silva (2003)
THERAPEUTIC PERSPECTIVE VIEW OF ANTIMICROBIAL PEPTIDES
P. Bala (2014)
A GxxxG-like Motif within HIV-1 Fusion Peptide Is Critical to Its Immunosuppressant Activity, Structure, and Interaction with the Transmembrane Domain of the T-cell Receptor*
Omri Faingold (2012)
Direct comparison of membrane interactions of model peptides composed of only Leu and Lys residues
R. Epand (2003)
Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides.
Y. Shai (1999)
Improved erythrocyte lysis assay in microtitre plates for sensitive detection and efficient measurement of haemolytic compounds from ichthyotoxic algae
E. Eschbach (2001)See more