|
1. |
Editorial |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 549-549
Claudio Toniolo,
Kyung‐Soo Hahm,
Lorenzo Stella,
Preview
|
PDF (35KB)
|
|
ISSN:1075-2617
DOI:10.1002/psc.1163
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
2. |
Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 550-558
Gianfranco Bocchinfuso,
Antonio Palleschi,
Barbara Orioni,
Giacinto Grande,
Fernando Formaggio,
Claudio Toniolo,
Yoonkyung Park,
Kyung‐Soo Hahm,
Lorenzo Stella,
Preview
|
PDF (549KB)
|
|
摘要:
AbstractMost antimicrobial peptides exert their activity by interacting with bacterial membranes, thus perturbing their permeability. They are investigated as a possible solution to the insurgence of bacteria resistant to the presently available antibiotic drugs. However, several different models have been proposed for their mechanism of membrane perturbation, and the molecular details of this process are still debated. Here, we compare fluorescence spectroscopy experiments and molecular dynamics (MD) simulations regarding the association with lipid bilayers and lipid perturbation for two different amphiphilic helical antimicrobial peptides, PMAP‐23 and trichogin GA IV. PMAP‐23, a cationic peptide member of the cathelicidin family, is considered to induce membrane permeability according to the Shai‐Matsuzaki‐Huang “carpet” model, while trichogin GA IV is a neutral peptide, member of the peptaibol family. Although several lines of evidence suggest a “barrel‐stave” mechanism of pore formation for the latter peptide, its length is only half the normal thickness of a lipid bilayer. Both fluorescence spectroscopy experiments and MD simulations indicated that PMAP‐23 associates with membranes close to their surface and parallel to it, and in this arrangement it causes a severe perturbation to the bilayer, both regarding its surface tension and lipid order. By contrast, trichogin GA IV can undergo a transition from a surface‐bound state to a transmembrane orientation. In the first arrangement, it does not cause any strong membrane perturbation, while in the second orientation it might be able to span the bilayer from one side to the other, despite its relatively short length, by causing a significant thinning of the membrane. Copyright © 2009 European Peptide Society an
ISSN:1075-2617
DOI:10.1002/psc.1144
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
3. |
Design of potent 9‐mer antimicrobial peptide analogs of protaetiamycine and investigation of mechanism of antimicrobial action |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 559-568
Soyoung Shin,
Jin‐Kyoung Kim,
Jee‐Young Lee,
Ki‐Woong Jung,
Jae‐Sam Hwang,
Juneyoung Lee,
Dong Gun Lee,
Iksoo Kim,
Song Yub Shin,
Yangmee Kim,
Preview
|
PDF (322KB)
|
|
摘要:
AbstractProtaetiamycine is an insect defensin, a naturally occurring 43‐amino‐acid‐residue antimicrobial peptide derived from the larvae of the beetleProtaetia brevitarsis. In a previous work that aimed at developing short antibiotic peptides, we designed 9‐mer peptide analogs of protaetiamycine. Among them, RLWLAIGRG‐NH2showed good antifungal activity againstCandida albicans.In this study, we designed four 9‐mer peptide analogs based on the sequence of RLWLAIGRG‐NH2, in which Gly or Ile was substituted with Arg, Lys, or Trp to optimize the balance between the hydrophobicity and cationicity of the peptides and to increase bacterial cell selectivity. We measured their toxicity to bacteria and mammalian cells as well as their ability to permeabilize model phospholipid membranes. Substitution of Arg for Gly9 at theC‐terminus (9Pbw1) resulted in two‐ to fourfold improvement in antibacterial activity. Further substitution of Gly7 with Lys (9Pbw2 and 9Pbw4) caused four‐ to eightfold improvement in the antibacterial activity without increase in cytotoxocity, while substitution of Gly7 with Trp (9Pbw3) increased cytotoxicity as well as antibacterial activity. The peptides 9Pbw2 and 9Pbw4 with the highest bacterial cell selectivity were not effective in depolarizing the membrane ofStaphylococcus aureuscytoplasmic membranes and showed almost no leakage of a fluorescent dye entrapped within the vesicles. Gel‐retardation experiments indicated that 9Pbw2 and 9Pbw4 inhibited the migration of DNA at concentrations>20 µM. Three positively charged residues at theC‐terminus in 9Pbw2 and 9Pbw4 may facilitate effective penetration into the negatively charged phospholipid membrane of bacteria. The results obtained in this study suggest that the bactericidal action of our potent antibacterial peptides, namely 9Pbw2 and 9Pbw4, may be attributed to the inhibition of the functions of intracellular components after penetration of the bacterial cell membrane. Copyright © 2009 European Peptide Society
ISSN:1075-2617
DOI:10.1002/psc.1156
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
4. |
Cell selectivity and mechanism of action of short antimicrobial peptides designed from the cell‐penetrating peptide Pep‐1 |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 569-575
Wan Long Zhu,
Kyung‐Soo Hahm,
Song Yub Shin,
Preview
|
PDF (208KB)
|
|
摘要:
AbstractPep‐1‐K (PK) is a good cell‐selective antimicrobial peptide designed from cell‐penetrating peptide Pep‐1. To develop novel short antimicrobial peptides with higher cell selectivity and shorter length compared with PK, several PK analogs were designed by the deletion, addition and/or substitution of amino acids. Among these analogs, PK‐12‐KKP (KKPWWKPWWPKWKK) showing the sequence and structure homology with a Trp/Pro‐rich natural antimicrobial peptide, indolicidin (IN), displayed a 20‐fold higher cell selectivity as compared to IN. Circular dichroism analysis revealed that PK‐12‐KKP adopts a folded structure combined with some portions of unordered structure. PK‐12‐KKP selectively binds to negatively charged bacterial membrane–mimetic vesicles, and its high phospholipid selectivity corresponds well with its high cell selectivity. Moreover, it showed very weak potential in depolarization of the cytoplasmic membrane ofStaphylococcus aureusat 8 µM(4× minimal inhibitory concentration) and dye leakage from negatively charged liposomes. These results suggest that the ultimate target of our designed PK‐12‐KKP maybe the intracellular components (e.g. protein, DNA or RNA) rather than the cytoplasmic membranes. Collectively, our designed short Trp/Pro‐rich peptide, PK‐12‐KKP, appears to be an excellent candidate for future development as a novel antimicrobial agent. Copyright © 2009 European
ISSN:1075-2617
DOI:10.1002/psc.1145
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
5. |
Structure dependence of biological activities for primate cathelicidins |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 576-582
Linda Tomasinsig,
Francesca Morgera,
Nikolinka Antcheva,
Sabrina Pacor,
Barbara Skerlavaj,
Margherita Zanetti,
Alessandro Tossi,
Preview
|
PDF (246KB)
|
|
摘要:
AbstractWe have analysed the effects of variations in orang‐utan (ppy), rhesus macaque (mmu) and leaf eater (pob) monkey orthologues of the human cathelicidin LL‐37, on a range of relevant biological activities. These host defence peptides range in cationicity from +4 to +10, and while the more cationicpobandmmuRL‐37 are in a monomeric and unstructured form in bulk solution (F‐form), the human andppyLL‐37 are in an aggregated/helical form (A‐form). Thein vitroantibacterial activity depended strongly on both the structural form and the charge. F‐form peptides were more potent against Gram‐positive and ‐negative bacteria and less salt, medium or serum sensitive than A‐form ones. CD studies suggested that A‐ and F‐form peptides interact with LPS in different manners, but the ability to detoxify it did not correlate directly with either the charge or structure. Toxicity towards eukaryotic cells also showed a varied dependence on the peptides' physical characteristics. Haemolytic activity was similar for all the tested peptides while other cytotoxicity assays revealed the highly cationic, F‐formpobRL‐37 as the most toxic, followed by the A‐form human LL‐37. As shown with the human peptide, toxicity depended markedly on the nature and metabolic state of the target cell. Our results suggest that different evolutionary trajectories for each orthologue lead to distinct sets of physical characteristics, which significantly differentiates their biological activities. Copyright © 2009 European Peptide
ISSN:1075-2617
DOI:10.1002/psc.1143
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
6. |
De novogeneration of antimicrobial LK peptides with a single tryptophan at the critical amphipathic interface |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 583-588
Su‐Jin Kang,
Hyung‐Sik Won,
Wahn‐Soo Choi,
Bong‐Jin Lee,
Preview
|
PDF (157KB)
|
|
摘要:
AbstractDe novodesign of amphipathic model peptides has been successful for generating many antimicrobial peptides with various lengths and amino acid compositions. Here, we suggest a very simple strategy to design antimicrobial peptides with a short length and a simple amino acid composition. Amphipathic helical properties were conferred by using only leucines and lysines and a single tryptophan was positioned at the critical amphipathic interface between the hydrophilic ending side and the hydrophobic starting side, in the helical wheel projection. According to this rule, the model peptides with 7 to 13 residues exhibited antimicrobial activity. Among them, the most potent activity against both Gram‐positive and Gram‐negative bacteria, covering all of the nine bacterial strains tested in this study, was found for the 11‐mer sequences having a 1:1 (L5K5W6) or a 3:2 (L6K4W6) ratio of leucines to lysines. In particular, the former peptide L5K5W6could be evaluated as the most useful agent, as it showed no significant hemolytic activity with a broad‐spectrum of antimicrobial activity. Copyright © 2009 European Peptide Society and John Wiley&S
ISSN:1075-2617
DOI:10.1002/psc.1149
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
7. |
Effect of Leucine and Lysine substitution on the antimicrobial activity and evaluation of the mechanism of the HPA3NT3 analog peptide |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 589-594
Ramamourthy Gopal,
Seong‐Cheol Park,
Kyeoung‐Ju Ha,
Seung Joo Cho,
Si Wouk Kim,
Peter I. Song,
Jae‐Woon Nah,
Yoonkyung Park,
Kyung‐Soo Hahm,
Preview
|
PDF (301KB)
|
|
摘要:
AbstractIn this study, a HPA3NT3‐analog (FKKLKKLFKKILKLK‐NH2) peptide was designed. In this analog, two Trp residues (positions 12, 14) were replaced with Leu, and Arg and Asn (positions 3, 13) were replaced with Lys to investigate the role of amino acid substitution and increased cationicity on antimicrobial and hemolytic activities. In fungal and Gram‐negative bacterial cells, HPA3NT3‐analog activity was unchanged or slightly enhanced when compared to the HPA3NT3 peptide. In addition, a twofold decrease in activity against Gram‐positive bacteria was observed. The HPA3NT3‐analog also induced less hemolysis (4.2%) than the HPA3NT3 peptide (71%) at 200 µM. Circular dichroism (CD) spectra revealed that the HPA3NT3‐analog peptide had an unordered structure in buffer and egg yolk L‐2‐phosphatidyl choline (EYPC), but adapted an α‐helical conformation in 50% 2,2,2‐trifluoroethanol (TFE) and negatively charged egg yolk L‐2‐phosphatidyl glycerol (EYPG), while the parent peptide showed an ordered structure in the EYPC. Additionally, the HPA3NT3‐analog peptide induced the leakage of calcein from egg yolk L‐2‐phosphatidyl ethanolamine (EYPE)/EYPG (7:3 w/w) large unilamellar vesicles (LUVs); however, the activity was slightly weaker than that of the HPA3NT3 peptide. The molecular dynamics (MD) structures revealed that the amino acid substitutions induced a significant variation in peptide structure. These results suggest that the substitutions of Arg and Asn with Lys and two Trp with Leu resulted in small changes in HPA3NT3‐analog activity and significant decreases in hemolytic activity. Copyright © 2009 European Pept
ISSN:1075-2617
DOI:10.1002/psc.1155
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
8. |
Activity of antimicrobial peptides in the presence of polysaccharides produced by pulmonary pathogens |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 595-600
M. Benincasa,
M. Mattiuzzo,
Y. Herasimenka,
P. Cescutti,
R. Rizzo,
R. Gennaro,
Preview
|
PDF (247KB)
|
|
摘要:
AbstractAntimicrobial peptides (AMPs) are secreted in the airway and contribute to initial defence against inhaled pathogens. Infections of the respiratory tract are a major cause of morbidity and mortality in preterm newborns and in patients with cystic fibrosis (CF). In this latter group, the state of chronic lung infection is due to the ability of bacteria to grow as mucoid biofilm, a condition characterised by overproduction and release of polysaccharides (PSs). In this study, we investigate the effect of PSs produced by lung pathogens such asPseudomonas aeruginosa, Klebsiella pneumoniaeand members of theBurkholderia cepaciacomplex on the antibacterial activity of structurally different peptides. The AMPs tested in this study include the cathelicidin LL‐37 and the β‐defensin hBD‐3 from humans, both released at the alveolar level, as well as peptides from other mammals, i.e. SMAP‐29, PG‐1 and Bac7(1‐35). Susceptibility assays, time killing and membrane permeabilization kinetics experiments were carried out to establish whether PSs produced by lung pathogens may be involved in the poor defence reaction of infected lungs and thus explain infection persistence. All the PSs investigated inhibited, albeit to a different extent, the antibacterial activity of the peptides tested, suggesting that their presence in the lungs of patients with CF may contribute to the decreased defence response of this district upon infection by PS‐producing microorganisms. The results also show that inhibition of the antibacterial activity is not simply due to ionic interaction between the negatively charged PSs and the cationic AMPs, but it also involves other structural features of both interactors. Copyright © 2009 European Peptide Society and John
ISSN:1075-2617
DOI:10.1002/psc.1142
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
9. |
Cell selectivity‐membrane phospholipids relationship of the antimicrobial effects shown by pleurocidin enantiomeric peptides |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 601-606
Juneyoung Lee,
Cana Park,
Seong‐Cheol Park,
Eun‐Rhan Woo,
Yoonkyung Park,
Kyung‐Soo Hahm,
Dong Gun Lee,
Preview
|
PDF (155KB)
|
|
摘要:
AbstractPreviously, we investigated the antimicrobial properties of pleurocidin (Ple) enantiomers. Our studies showed that theL‐enantiomer exhibited about a 2–16 fold more potent activity against bacterial strains as compared to that of theD–enantiomer. However, fungal strains were about two–fold more susceptible to theD–enantiomer than to theL‐enantiomer. In this study, confocal laser scanning microscopy indicates that the Ple enantiomers internalize into the cell surface. The present results also suggest that they could be characterized by a membrane–active mechanism. To further elucidate their selective membranolytic activities, we conducted a fluorescence analysis. A study with 1,6–diphenyl–1,3,5–hexatriene, a hydrophobic molecule, showed that theL–and theD–enantiomer exert more potent antibacterial or antifungal activity than their opposite enantiomer, respectively. Furthermore, we synthesized liposomes by using representative phospholipids consisting of bacterial or fungal membranes. Our results show that theL‐enantiomer causes significant dye leakage from negatively charged liposomes (PG/CL; 58:42, PC/PG; 1:1, w/w) which mimic bacterial membranes such asStaphylococcus aureus. Conversely, theD–enantiomer has more potent leakage effects against fungal liposomes (PC/PE/PI/ergosterol; 5:4:1:2, w/w/w/w, PC/ergosterol; 10:1, w/w). In summary, these results suggest that the selective antimicrobial effects of the Ple enantiomers against bacterial and fungal cells may be due to the different lipid compositions of prokaryotes and eukaryotes. Copyright © 2009 European Peptide Soci
ISSN:1075-2617
DOI:10.1002/psc.1157
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
10. |
Esculentin 1–21: a linear antimicrobial peptide from frog skin with inhibitory effect on bovine mastitis‐causing bacteria |
|
Journal of Peptide Science,
Volume 15,
Issue 9,
2009,
Page 607-614
Alfonso Enrique Islas‐Rodrìguez,
Ludovica Marcellini,
Barbara Orioni,
Donatella Barra,
Lorenzo Stella,
Maria Luisa Mangoni,
Preview
|
PDF (203KB)
|
|
摘要:
AbstractMastitis, or inflammation of the mammary gland, is the most common and expensive illness of dairy cows throughout the world. Although stress and physical injuries may give rise to inflammation of the udders, infections by bacteria or other microorganisms remain the major cause, and infusion of antibiotics is the main treatment approach. However, the increased emergence of multidrug‐resistant pathogens and the production of milk contaminated with antibiotics has become a serious threat in the livestock. Hence, there is an urgent need for the discovery of new therapeutic agents with a new mode of action. Gene‐encoded AMPs, which represent the first line of defence in all living organisms, are considered as promising candidates for the development of new anti‐infective agents. This paper reports on the antibacterial activitiesin vitroand in an animal model, of the frog skin AMP esculentin 1–21 [Esc(1–21)], along with a plausible mode of action. Our data revealed that this peptide (i) is highly potent against the most common mastitis‐causing microbes (e.g.Streptococcus agalactiae); and (ii) is activein vivo, causing a visible regression of the clinical stage of mastitis in dairy cows, after 1 week of peptide treatment. Biophysical characterisation revealed that the peptide adopts an α‐helical structure in microbial mimicking membranes and is able to permeate the membrane ofS. agalactiaein a dose‐dependent manner. Overall, these data suggest Esc(1–21) as an attractive AMP for the future design of new antibiotics to cure mastitis in cattle. Copyright © 2009 European Peptide Society and J
ISSN:1075-2617
DOI:10.1002/psc.1148
出版商:John Wiley&Sons, Ltd.
年代:2009
数据来源: WILEY
|
|