Mode of action of membrane lysis by custom lytic peptides and the local stability of protein

2001 ◽  
Author(s):  
King Wong Leung
Keyword(s):  
Mode Of Action ◽  
Local Stability ◽  
Membrane Lysis ◽  
Lytic Peptides

Kinetics of membrane lysis by custom lytic peptides and peptide orientations in membrane

2001 ◽  
Vol 268 (6) ◽  
pp. 1659-1669 ◽  
Author(s):  
H. M. Chen ◽  
A. H. A. Clayton ◽  
W. Wang ◽  
W. H. Sawyer
Keyword(s):  
Membrane Lysis ◽  
Lytic Peptides ◽  
Kinetics Of

scholarly journals Androctonin, a hydrophilic disulphide-bridged non-haemolytic anti-microbial peptide: a plausible mode of action

2000 ◽  
Vol 345 (3) ◽  
pp. 653-664 ◽  
Author(s):  
Charles HETRU ◽  
Lucienne LETELLIER ◽  
Ziv OREN ◽  
Jules A. HOFFMANN ◽  
Yechiel SHAI
Keyword(s):  
Mode Of Action ◽  
Cell Envelope ◽  
Acyl Chain ◽  
Lipid Vesicles ◽  
Attenuated Total Reflection ◽  
Haemolytic Activity ◽  
Bacterial Membranes ◽  
Slow Kinetics ◽  
High Concentrations ◽  
Lytic Peptides

Androctonin is a 25-residue non-haemolytic anti-microbial peptide isolated from the scorpion Androctonus australis and contains two disulphide bridges. Androctonin is different from known native anti-microbial peptides, being a relatively hydrophilic and non-amphipathic molecule. This raises the possibility that the target of androctonin might not be the bacterial membrane, shown to be a target for most amphipathic lytic peptides. To shed light on its mode of action on bacteria and its non-haemolytic activity, we synthesized androctonin, its fluorescent derivatives and its all-D-amino acid enantiomer. The enantiomer preserved high activity, suggesting a lipid-peptide interaction between androctonin and bacterial membranes. In Gram-positive and (at higher concentrations) Gram-negative bacteria, androctonin induced an immediate perturbation of the permeability properties of the cytoplasmic membrane of the bacterial energetic state, concomitant with perturbation of the morphology of the cell envelope as revealed by electron microscopy. Androctonin binds only to negatively charged lipid vesicles and induces the leakage of markers at high concentrations and with a slow kinetics, in contrast with amphipathic α-helical anti-microbial peptides that bind and permeate negatively charged vesicles, and to a smaller extent also zwitterionic ones. This might explain the selective lytic activity of androctonin towards bacteria but not red blood cells. Polarized attenuated total reflection-Fourier transform infrared spectroscopy revealed that androctonin adopts a β-sheet structure in membranes and did not affect the lipid acyl chain order, which supports a detergent-like effect. The small size of androctonin, its hydrophilic character and its physicochemical properties are favourable features for its potential application as a replacement for commercially available antibiotics to which bacteria have developed resistance.

scholarly journals Kinetics of membrane lysis by custom lytic peptides and peptide orientations in membrane

2001 ◽  
Vol 268 (6) ◽  
pp. 1659-1669 ◽  
Author(s):  
H. M. Chen ◽  
A. H. A. Clayton ◽  
W. Wang ◽  
W. H. Sawyer
Keyword(s):  
Membrane Lysis ◽  
Lytic Peptides ◽  
Kinetics Of

Phospholipid-dependent changes in membrane permeability induced by staphylococcal δ-lysin and bee venom melittin

1985 ◽  
Vol 63 (1) ◽  
pp. 1-6 ◽  
Author(s):  
M. Bhakoo ◽  
T. H. Birkbeck ◽  
J. H. Freer
Keyword(s):  
Dose Response ◽  
Mode Of Action ◽  
Response Curve ◽  
Atp Release ◽  
Cell Types ◽  
Bee Venom ◽  
Degree Of Saturation ◽  
Large Unilamellar Vesicles ◽  
Concentration Sensitivity ◽  
Lytic Peptides

The effect of purified staphylococcal δ-lysin and bee venom melittin on the permeability of large unilamellar vesicles (liposomes) composed of structurally defined lipids was investigated by following release of sequestered ATP using a bioluminescent assay. ATP release was linearly related to the logarithm of the peptide concentration. Sensitivity to the lytic peptides, as measured by the release of ATP and the slope of the dose–response curve, depended on the chain length and the degree of saturation of the hydrocarbon substituents of the phospholipid in the vesicles. Neither the sign of the surface charge nor the presence of sterol had any significant effect on the sensitivity of liposomes to peptide-induced lysis. Release of ATP and haemoglobin from intact sheep and cod erythrocytes was also determined after their exposure to δ-lysin and melittin. Both cell types showed similar degrees of sensitivity to each lytic peptide when ATP release was followed, but the release of haemoglobin from sheep erythrocytes by δ-lysin was much less than from cod erythrocytes. The implications of these results on the mode of action of the two agents are discussed.

scholarly journals Controlled alteration of the shape and conformational stability of α-helical cell-lytic peptides: effect on mode of action and cell specificity

2005 ◽  
Vol 390 (1) ◽  
pp. 177-188 ◽  
Author(s):  
Igor Zelezetsky ◽  
Sabrina Pacor ◽  
Ulrike Pag ◽  
Niv Papo ◽  
Yechiel Shai ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Structural Characteristics ◽  
Conformational Stability ◽  
Helical Structure ◽  
Close Correlation ◽  
Model Systems ◽  
Host Cells ◽  
Helical Conformation ◽  
Novel Method ◽  
Lytic Peptides

A novel method, based on the rational and systematic modulation of macroscopic structural characteristics on a template originating from a large number of natural, cell-lytic, amphipathic α-helical peptides, was used to probe how the depths and shapes of hydrophobic and polar faces and the conformational stability affect antimicrobial activity and selectivity with respect to eukaryotic cells. A plausible mode of action explaining the peptides' behaviour in model membranes, bacteria and host cells is proposed. Cytotoxic activity, in general, correlated strongly with the hydrophobic sector depth, and required a majority of aliphatic residue side chains having more than two carbon atoms. It also correlated significantly with the size of polar sector residues, which determines the penetration depth of the peptide via the so-called snorkel effect. Both an oblique gradient of long to short aliphatic residues along the hydrophobic face and a stabilized helical structure increased activity against host cells but not against bacteria, as revealed by haemolysis, flow cytofluorimetric studies on lymphocytes and surface plasmon resonance studies with model phosphatidylcholine/cholesterol membranes. The mode of interaction changes radically for a peptide with a stable, preformed helical conformation compared with others that form a structure only on membrane binding. The close correlation between effects observed in biological and model systems suggests that the ‘carpet model’ correctly represents the type of peptides that are bacteria-selective, whereas the behaviour of those that lyse host cells is more complex.

Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

1971 ◽  
Vol 29 ◽  
pp. 570-571
Author(s):  
E. A. Elfont ◽  
R. B. Tobin ◽  
D. G. Colton ◽  
M. A. Mehlman
Keyword(s):  
Chemical Composition ◽  
Rat Liver ◽  
Future Study ◽  
Mode Of Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Effective Inhibitor ◽  
Biochemical Effects ◽  
Glycerophosphate Dehydrogenase ◽  
Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

Mode of action of 6-oxophenolic triterpenoids against Bacillus subtilis

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
L Moujir ◽  
L de León ◽  
IL Bazzocchi
Keyword(s):  
Bacillus Subtilis ◽  
Mode Of Action
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