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LF f(17-31) [id=LFB0031]

Producer Organism : Native Protein : Production Method :
Cow Lactoferrin (LF) Synthetic
Activity : Antibacterial, antifungal
Target Organisms :

Gram-positive: Lactobacillus brevis CECT216 (MIC=25 mg/ml), Lactobacillus hilgardii CECT4659 (MIC=200 mg/ml), Pediococcus damnosus CECT4693 (MIC=6.3 mg/ml), Oenococcus oeni (MIC=200 mg/ml), Staphylococcus aureus ATCC 25923 (MIC=48-50 ÁM), Bacillus subtilis CECT498 (MIC=16 ÁM).

Gram-negative: Escherichia coli ATCC 25922 (MIC=20-24 ÁM), Escherichia coli K12 D21e19 (MIC=160 ÁM), Escherichia coli K12 D21e7 (MIC=40 ÁM), Escherichia coli K12 W3110 (MIC=160 ÁM), Escherichia coli K12 D21 (MIC=160 ÁM), Escherichia coli K12 D21f1 (MIC=1280 ÁM), Escherichia coli K12 D21f2 (MIC=1280 ÁM), Escherichia coli MLK53 (MIC=160 ÁM), Escherichia coli MLK1067 (MIC=160 ÁM), Escherichia coli MLK986 (MIC=40 ÁM), Escherichia coli WA707 (MIC=160 ÁM), Escherichia coli WA834 (MIC=160 ÁM), Escherichia coli DH5a (MIC=48 ÁM).

Yeast: Active against Saccharomyces cerevisiae Maurivin AWRI350, Dekkera bruxellensis wild strain, Pichia membranifaciens wild strain, Zygosaccharomyces bailii wild strain, Zygosaccharomyces bisporus wild strain at 16 ÁM, Dekkera bruxellensis 531 (MIC=20 ÁM), Saccharomyces cerevisiae FY1679 (MIC=32 ÁM), Dekkera bruxellensis 928 (MIC=3.75 ÁM), Dekkera bruxellensis 1327 (MIC=7.5 ÁM), Dekkera bruxellensis 1700 (MIC=20 ÁM), Dekkera bruxellensis 1701 (MIC=20 ÁM), Dekkera bruxellensis 1717 (MIC=20 ÁM), Dekkera bruxellensis 2114 (MIC=10 ÁM), Dekkera bruxellensis 2174 (MIC=7.5 ÁM), Dekkera bruxellensis F11 (MIC=5 ÁM).

Filamentous fungi: Penicillium digitatum PHI-26 (MIC=4 ÁM), Penicillium italicum PHI-1 (MIC=4 ÁM), Penicillium expansum PHI-65 (MIC=8 ÁM), Penicillium sp. PHI-8 (MIC=8 ÁM), Alternaria sp. PHI-44 (MIC=16 ÁM), Aspergillus nidulans biA1 (MIC=4 ÁM), Botrytis cinerea 8 (MIC=16 ÁM), Fusarium oxysporum CECT2866 (MIC=8 ÁM).

NOTE: No activity against Cryptococcus albidus wild strain (>16 ÁM), Magnaporthe grisea PR-9 (>32 ÁM) .

Description :
Production method: Synthetic.


LFB0031 is a 15-residue linear antimicrobial peptide derived from bovine lactoferricin (LFB0084), which has antimicrobial activity similar to that of the intact 25-residue disulfide-cyclized peptide. This supports the observation that the antimicrobial potency of LfcinB does not require the single disulfide bond (Citation:1).
This peptide is used to study the structureľfunction relationship of LFB and the importance of the 2 Trp residues (Citation:1, 6, 7, 8, 9, 12).
An alignment analysis using MegAlign software, Clustal method, showed that LFP0001, LFH0022, LFM0001 and LAG0002 had similarity indexes with LFB0031 of 33%, 40%, 53% and 67%, respectively. The antibacterial activities reveal that LFB0031 was remarkably more active than the other lactoferricin peptides. It is noteworthy that LAG0003 was the only lactoferricin peptide besides LFB with a measurable MIC value against E. coli (Citation 6).
Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence (LFH0016, LFH0017, LFH0018, LFH0019 and LFH0020) and peptides corresponding to chimeras of human (LFH0081 and LFH0082) and bovine sequences (LFB0031, LFB0041 and LFB0046). None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity (Citation: 10).
Length : 15 Mass (Da): 1 994.83 Common Amino Acids : KR
Isolectric Point : 12.26 Net Charge : 6 Absent Amino Acids : DEHINPSTVY
Basic Residues : 6 Acidic Residues : 0 Hydrophobic Residues : 5
Polar Residues : 2 Boman Index : -48.01 Hydropathy Index : -1.207
Aliphatic Index : 32.67 Instability Index : 0 Extinction Coefficient : 11000
Absorbance 280nm : 785.71

Wheel representation

Hydrophobicity plot

Red solid plot : values according to the hydrophobicity scale of Kyte and Doolittle (reference paper).
Yellow dashed plot : Experimentally determined hydrophobicity scale for proteins at membrane interfaces(reference paper).
Green dotted-dashed plot : prediction of transmembrane helices (reference paper). In this scale (unlike the others), more negative values reflect greater hydrophobicity.

Multiple Sequence Alignment (MSA)


                      1 [        .         .         . ] 32
  1 LFBNATIVE 100.0%    FKCRRWQWRMKKLGAPSITCVRRAFALECIRA   
  2 LFB0017   100.0%    FKCRRWQWR-----------------------   
  3 LFB0043    93.3%    FKCRRWQWRAKKLGA-----------------   
  4 LFB0052    86.7%    FKCWRWQWRWKKLGA-----------------   
  5 LFB0037    93.3%    FKCARWQWRMKKLGA-----------------   
  6 LFB0040    93.3%    FKCRRWAWRMKKLGA-----------------   
  7 LFB0038    93.3%    FKCRAWQWRMKKLGA-----------------   
  8 LFB0088    96.0%    FKCRRWQWRMKKLGAPSITCVRRAE-------   
  9 LFB0039    93.3%    FKCRRAQWRMKKLGA-----------------   
 10 LFB0062    93.3%    FKCRRAQWRMKKLGA-----------------   
 11 LFB0072    93.3%    FKCRRAQWRMKKLGA-----------------   
 12 LFB0075    93.3%    FKCRRAQWRMKKLGA-----------------   
 13 LFB0078    93.3%    FKCRRAQWRMKKLGA-----------------   
 14 LFB0064    86.7%    FKCRRAQARMKKLGA-----------------   
 15 LFB0117    54.5%    ---RRAAARAKKAG------------------   
 16 LFB0080    86.7%    FKCRRAQARMKKLGA-----------------   
 17 LFB0074    86.7%    FKCRRAQARMKKLGA-----------------   
 18 LFB0077    86.7%    FKCRRAQARMKKLGA-----------------   
 19 LFB0056    93.3%    FKCRRFQWRMKKLGA-----------------   
 20 LFB0059    93.3%    FKCRRFQWRMKKLGA-----------------   
 21 LFB0053    93.3%    FKCRRFQWRMKKLGA-----------------   
 22 LFB0081    93.3%    FKCRRFQWRMKKLGA-----------------   
 23 LFB0055    86.7%    FKCRRFQFRMKKLGA-----------------   
 24 LFB0058    86.7%    FKCRRFQFRMKKLGA-----------------   
 25 LFB0061    86.7%    FKCRRFQFRMKKLGA-----------------   
 26 LFB0083    86.7%    FKCRRFQFRMKKLGA-----------------   
 27 LFB0041    93.3%    FKCRRWQARMKKLGA-----------------   
 28 LFB0063    93.3%    FKCRRWQARMKKLGA-----------------   
 29 LFB0076    93.3%    FKCRRWQARMKKLGA-----------------   
 30 LFB0079    93.3%    FKCRRWQARMKKLGA-----------------   
 31 LFB0073    93.3%    FKCRRWQARMKKLGA-----------------   
 32 LFB0060    93.3%    FKCRRWQFRMKKLGA-----------------   
 33 LFB0082    93.3%    FKCRRWQFRMKKLGA-----------------   
 34 LFB0057    93.3%    FKCRRWQFRMKKLGA-----------------   
 35 LFB0054    93.3%    FKCRRWQFRMKKLGA-----------------   
 36 LFB0042    93.3%    FKCRRWQWAMKKLGA-----------------   
 37 LFB0115    81.8%    ---RRWQRWMKKLG------------------   
 38 LFB0033   100.0%    FKCRRWQWRMKKLGA-----------------   
 39 LFB0032   100.0%    FKCRRWQWRMKKLGA-----------------   
 40 LFB0031   100.0%    FKCRRWQWRMKKLGA-----------------   
 41 LFB0050    86.7%    FKWRRWQWRMKKLWA-----------------   
 42 LFB0051    80.0%    FKWRRWWWRMKKLWA-----------------   
 43 LFB0049    93.3%    FKCRRWQWRMKKLWA-----------------   
 44 LFB0018   100.0%    FKCRRWQWRM----------------------   
 45 LFB0020   100.0%    FKCRRWQWRMK---------------------   
 46 LFB0045    93.3%    FKCRRWQWRMKALGA-----------------   
 47 LFB0044    93.3%    FKCRRWQWRMAKLGA-----------------   
 48 LFB0097   100.0%    ---RRWQWR-----------------------   
 49 LFB0030   100.0%    FKCRRWQWRMKKLG------------------   
 50 LFB0087   100.0%    FKCRRWQWRMKKLGAPSITCVRRAF-------   
 51 LFB0024    54.5%    YKAWRWAWRWK---------------------   
 52 LFB0025    54.5%    YKAWRWAWRWK---------------------   
 53 LFB0027    36.4%    YRMWRWAWRWR---------------------   
 54 LFB0028    36.4%    YRMWRWRWRWR---------------------   
 55 LFB0026    36.4%    YRAWRWAWRWR---------------------   
 56 LFB0023    63.6%    YKARRWAWRWK---------------------   
 57 LFB0022    72.7%    YKARRWAWRMK---------------------   
 58 LFB0021    81.8%    FKARRWAWRMK---------------------   
 59 LFB0019    90.0%    FKARRWQWRM----------------------   
 60 LFB0036    93.3%    FKARRWQWRMKKLGA-----------------   
 61 LFB0070    93.3%    FKARRWQWRMKKLGA-----------------   
 62 LFB0069    93.3%    FKARRWQWRMKKLGA-----------------   
 63 LFB0068    93.3%    FKARRWQWRMKKLGA-----------------   
 64 LFB0065    93.3%    FKARRWQWRMKKLGA-----------------   
 65 LFB0106   100.0%    ---RRWQWRMKK--------------------   
 66 LFB0029    45.5%    RRWYRWAWRMR---------------------   
 67 LFB0118   100.0%    ----RWQWRM----------------------   
 68 LFB0113    81.8%    ---RRWQWRMRRLG------------------   
 69 LFB0112    72.7%    ---KKWQWKMKKLG------------------   
 70 LFB0114    81.8%    ---KKWQWRMKKLG------------------   
 71 LFB0116    54.5%    ---EEWQWEMEELG------------------   
 72 LFB0048    93.3%    FKWRRWQWRMKKLGA-----------------   
 73 LFB0090    92.0%    FKSRRWQWRMKKLGAPSITSVRRAF-------   
 74 LFB0110    18.2%    ----RRWQWRMKKLG-----------------   
 75 LFB0067    93.3%    FKFRRWQWRMKKLGA-----------------   
 76 LFB0071    93.3%    FKFRRWQWRMKKLGA-----------------   
 77 LFB0066    93.3%    FKFRRWQWRMKKLGA-----------------   
 78 LFB0108   100.0%    ---RRWQWRMKKL-------------------   
 79 LFB0102   100.0%    ---RRWQWRMKK--------------------   
 80 LFB0034    93.3%    AKCRRWQWRMKKLGA-----------------   
 81 LFB0111   100.0%    ---RRWQWRMKKLG------------------   
 82 LFB0104   100.0%    ---RRWQWRMKK--------------------   
 83 LFB0035    93.3%    FACRRWQWRMKKLGA-----------------   
 84 LFB0109   100.0%    ---RRWQWRMKKLG------------------   
 85 LFB0101   100.0%    ---RRWQWRMKK--------------------   
 86 LFB0046    93.3%    FKCRRWQWRMKKAGA-----------------   
 87 LFB0107   100.0%    ---RRWQWRMKK--------------------   
 88 LFB0100   100.0%    ---RRWQWRMKK--------------------   
 89 LFB0047    93.3%    FKCRRWQWRMKKLAA-----------------   
 90 LFB0098   100.0%    ---RRWQWRMKK--------------------   
 91 LFB0105   100.0%    ---RRWQWRMKK--------------------   
 92 LFB0103   100.0%    ---RRWQWRMKK--------------------   
 93 LFB0086   100.0%    FKCRRWQWRMKKLGAPSITCVRRAF-------   
 94 LFB0089   100.0%    FKCRRWQWRMKKLGAPSITCVRRAF-------   
 95 LFB0085   100.0%    FKCRRWQWRMKKLGAPSITCVRRAF-------   
 96 LFB0084   100.0%    FKCRRWQWRMKKLGAPSITCVRRAF-------   
 97 LFB0092   100.0%    FKCRRWQWRMKKLGAPSITCVRRAFA------   
 98 LFB0095   100.0%    -KCRRWQWRMKKLGAPSITCV-----------   
 99 LFB0096   100.0%    --CRRWQWRMKKLGAPSITCV-----------   

100 LFB0093   100.0%    FKCRRWQWRMKKLGAPSITCVRRAFAL-----   

101 LFB0091   100.0%    FKCRRWQWRMKKLGAPSITCVRRAFA------   

102 LFB0119   100.0%    ----------KKLGAPSITCVRRAFA------   
103 LFB0120   100.0%    -------------GAPSITCVRRAF-------   

104 LFB0121   100.0%    ----------------------------CIRA   
105 LFB0094   100.0%    FKCRRWQWRMKKLGAPSITCVRRAFALECIR-   

Citation: 1

Comparison of NMR structures and model-membrane interactions of 15-residue antimicrobial peptides derived from bovine lactoferricin

Cited Entries: LFB0031, LFB0039, LFB0041, LFB0088

Authors:Weiguo, J., Svendsen, J.S., Vogel, H.J.
Journal: Biochemistry & Cell Biology 2006, 84.
Abstract: LFB (FKCRRWQWRMKKLGA-HN2) is a 15-residue linear antimicrobial peptide derived from bovine lactoferricin, which has antimicrobial activity similar to that of the intact 25-residue disulfide-cyclized peptide. Previous alanine-scan studies, in which all of the residues in LFB were individually replaced with Ala, showed that the 2 tryptophan (Trp) residues of LFB were crucial to its antimicrobial activity. When either Trp6 or Trp8 was replaced with Ala (LFBA6 and LFBA8, respectively), these 2 peptides were almost devoid of antimicrobial activity. We determined the structures of LFB, LFBA6, and LFBA8 bound to membrane-mimetic SDS micelles using NMR spectroscopy, and studied their interactions with different phospholipid-model membranes. The membrane interactions of LFB exhibited little correlation with its antimicrobial activity, suggesting that the mechanism of action of LFB involves intracellular targets. However, the much higher antimicrobial activity of LFB compared with LFBA6 and LFBA8 might result, in part, from the formation of energetically favorable cation-pi interactions observed only in LFB. Information about the importance of Arg and Trp cation-pi interactions will provide insight for the future design of potent antimicrobial peptidomimetics.
Keywords: PEPTIDE antibiotics; Lactoferrin; FLUORESCENCE spectroscopy; NUCLEAR magnetic resonance; Phospholipids; Alanine; antimicrobial peptide; membrane mimetics; microcalorimetry; imitation de la membrane; microcalorimăŞtrie; peptide antimicrobien; răŞsonance magnăŞtique nuclăŞaire; spectroscopie ╚┐ fluorescence
Citation: 2

Post-antibiotic effect of the antimicrobial peptide lactoferricin on Escherichia coli and Staphylococcus aureus

Cited Entries: LFB0031, LFB0032, LFB0033, LFB0084

Authors:Haukland, H.H., Vorland, L.H.
Journal: Journal of Antimicrobial Chemotherapy 2001, 48(4).
Abstract: Lactoferricin is an antimicrobial peptide generated by gastric pepsin cleavage of lactoferrin. A possible post-antibiotic effect (PAE) of bovine lactoferricin (Lfcin B) and two shorter peptide derivatives against Staphylococcus aureus and Escherichia coli was studied. A drug removal technique involving centrifugation and washing was used. No PAE was found for Lfcin B against these two bacteria. The shorter derivatives had a short PAE against E. coli. They had a short negative PAE against S. aureus. In conclusion, the overall PAE is not overwhelming, but the small differences found between the different peptideg"bacteria combinations could indicate that different peptide mechanisms of action might be present.
Citation: 3

Antimicrobial action of synthetic peptides towards wine spoilage yeasts

Cited Entries: LFB0031, LFB0097

Authors:Enrique, M., Marcos, J.F., Yuste, M., Mart«ez, M., Valles, S., Manzanares, P.
Journal: International Journal of Food Microbiology 2007, 118(3).
CrossRef External Link
Abstract: The antimicrobial action of selected short synthetic peptides against wine spoilage yeasts such as Cryptococcus albidus, Dekkera bruxellensis, Pichia membranifaciens, Saccharomyces cerevisiae, Zygosaccharomyces bailii and Zygosaccharomyces bisporus has been examined. Peptides analyzed include nine sequence-related antifungal hexapeptides (PAFs) previously developed by a combinatorial approach, and two representative lactoferricin B (LfcinB)-derived peptides. Different peptides had distinct activity profiles. In vitro assays identified the peptides PAF26, PAF36, and LfcinB17ľ31, as having growth inhibitory properties towards several of the yeasts at low micromolar concentrations. Z. bailii and Z. bisporus were the most sensitive yeasts. In addition to their fungistatic activity, the three peptides showed fungicidal properties towards Z. bailii, Z. bisporus, and S. cerevisiae in laboratory growth medium. Remarkably, only LfcinB17ľ31 against Z. bisporus had inhibitory and fungicidal properties in wine at the concentrations assayed, showing that the antimicrobial action of each peptide is dependent on both the food matrix and the target micro-organism. Lack of fungicidal activity of peptides against Z. bailii in wine is related to the presence of salt ions other than divalent cations. On the contrary, fungicidal activity of LfcinB17ľ31 towards Z. bisporus was not significantly affected by wine salts. Our data identify a bioactive peptide from natural origin with potential use against the food spoilage yeast Z. bisporus, and indicate that the application of antimicrobial peptides in wine preservation deserves further investigation.
Keywords: antimicrobial peptide; Lactoferricin B-derived peptide; Spoilage yeasts; Wine; Zygosaccharomyces; S.cerevisiae
Citation: 4

Construction and synthesis of lactoferricin derivatives with enhanced antibacterial activity

Cited Entries: LFH0026, LFB0031, LFB0089, LFB0164, LFB0165, LFB0166, LFB0167, LFB0168, LFB0169, LFB0170, LFM0020, LAG0006

Authors:Rekdal, O., Andersen, J., Vorland, L.H., Svendsen, J.S.
Journal: Journal of Peptide Science 1999, 5(1): 32-45.
Abstract: A series of peptides derived from sequences from human, bovine, murine and caprine lactoferrin has been prepared and investigated for antibacterial effect. Among the four species investigated peptides based on the bovine sequence displayed significant activity. The bovine sequence, bovine lactoferricin, showed a MIC value of 30 μg/mL on E. coli and S. aureus, whereas the three other lactoferricins possessed MIC values above 200 μg/mL. Based on these findings, novel peptides with enhanced antibacterial activities, were prepared with sequences designed by molecular modelling and structure-activity studies.
Keywords: Lactoferricin; Antibacterial; sequence modification; Qsar; ACM,acetamidomethyl; LFB,bovine lactoferricin; LFH,human lactoferricin; LFC,caprine lactoferricin; LFM,murine lactoferricin; QSAR,quantitative structure activity relationship; PLS,projection to latent structures
Citation: 5

Inhibition of the wine spoilage yeast Dekkera bruxellensis by bovine lactoferrin-derived peptides

Cited Entries: LFB0031

Authors:Enrique, M., Marcos, J.F., Yuste, M., Martinez, M., Vallˇ, S., Manzanares, P.
Journal: International Journal of Food Microbiology 2008, 127(3).
CrossRef External Link
Abstract: The antimicrobial action of lactoferrin (LF)-derived peptides against Dekkera bruxellensis strains isolated from spoiled wines has been examined. The study included a fifteen-residue peptide (LfcinB17-31) derived from bovine lactoferricin B and a bovine LF pepsin hydrolysate (LFH). In vitro assays showed the inhibitory properties of LfcinB17-31 on D. bruxellensis growth with IC50 and MIC values in the micromolar range. Strains tested showed different sensitivity to the peptide. LfcinB17-31 showed fungicidal properties towards all strains tested in laboratory growth medium. However, the extent of fungicidal activity was strain-dependent in must and wine, confirming the different antimicrobial action of peptides depending on both the food matrix and the target micro-organism. The binding of LfcinB17-31 to D. bruxellensis cells was visualized by fluorescence microscopy and correlated with the fungicidal activity in the different matrixes. LfcinB17-31 and LFH showed growth inhibitory properties in wine suggesting their potential use for spoilage control.
Keywords: Dekkera bruxellensis; Wine spoilage; antimicrobial peptide; Lactoferrin-derived peptides; Binding activity
Citation: 6

Selectivity and antimicrobial action of bovine lactoferrin derived peptides against wine lactic acid bacteria

Cited Entries: LFH0008, LFB0031

Authors:Enrique, M., Manzanares, P., Yuste, M., Martinez, M., Valles, S., Marcos, J.F.
Journal: Food Microbiology 2009, 26(3).
CrossRef External Link
Abstract: In this study, the antibacterial activities of a bovine Lactoferrin pepsin hydrolysate (LFH) and a synthetic peptide derived from bovine lactoferricin (LfcinB17ľ31) have been evaluated against Oenococcus oeni and three additional lactic acid bacteria (LAB) known to cause spoilage during winemaking processes. Inhibition of bacterial growth was demonstrated in vitro in synthetic broth media (MRS) for both LFH and LfcinB17ľ31. The bactericidal activity of the synthetic peptide was also assayed and found to vary depending on the bacterial species and the matrix in which exposure to peptide occurred (either MRS broth or white must). Specificity of LfcinB17ľ31 for Lactobacillus brevis, Pediococcus damnosus, and O. oeni was demonstrated in must fermentation experiments in which these three LAB co-existed with the winemaking Saccharomyces cerevisiae T73 in the presence of the peptide. Finally, fermentation experiments also showed that LfcinB17ľ31 at inhibitory concentrations did not alter either fermentation kinetics or specific enological parameters.
Keywords: Antimicrobial peptides; L.brevis; L.hilgardii; P.damnosus; O.oeni; S.cerevisiae
Citation: 7

Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity

Cited Entries: LFB0031, LFB0048, LFB0049, LFB0050, LFB0051, LFB0052

Authors:Str°m, M.B., Haug, B.E., Rekdal, A., Skar, M.L., Stensen, W., Svendsen, J.S.
Journal: Biochemistry & Cell Biology 2002, 80.
Abstract: This review focuses on important structural features affecting the antimicrobial activity of 15-residue derivatives of lactoferricins. Our investigations are based on an alanine-scan of a 15-residue bovine lactoferricin derivative that revealed the absolute necessity of two tryptophan residues for antimicrobial activity. This "tryptophan-effect" was further explored in homologous derivatives of human, caprine, and porcine lactoferricins by the incorporation of one additional tryptophan residue, and by increasing the content of tryptophan in the bovine derivative to five residues. Most of the resulting peptides display a substantial increase in antimicrobial activity. To identify which molecular properties make tryptophan so effective, a series of bovine lactoferricin derivatives were prepared containing non-encoded unnatural aromatic amino acids, which represented various aspects of the physicochemical nature of tryptophan. The results clearly demonstrate that tryptophan is not unique since most of the modified peptides were of higher antimicrobial potency than the native peptide. The size and three-dimensional shape of the inserted "super-tryptophans" are the most important determinants for the high antimicrobial activity of the modified peptides. This review also describes the use of a "soft-modeling" approach in order to identify important structural parameters affecting the antimicrobial activity of modified 15-residue murine lactoferricin derivatives. This QSAR-study revealed that the net charge, charge asymmetry, and micelle affinity of the peptides were the most important structural parameters affecting their antimicrobial activity.
Keywords: Lactoferrin; IRON proteins; ANTI-infective agents; peptides; AMINO acids; acides aminăŞs aromatiques non codăŞs; Antimicrobial peptides; Lactoferricin; lactoferricine; non-encoded aromatic amino acids; peptides antimicrobiens; tryptophan; tryptophane
Citation: 8

Antibacterial activity of 15-residue lactoferricin derivatives

Cited Entries: LFH0022, LFH0023, LFB0031, LFB0034, LFB0035, LFB0036, LFB0037, LFB0038, LFB0039, LFB0040, LFB0041, LFB0042, LFB0043, LFB0044, LFB0045, LFB0046, LFB0047, LAG0002, LAG0003, LFP0001, LFP0002, LFM0001, LFM0002

Authors:Str°m, M.B., Svendsen, J.S., Rekdal, O.
Journal: The Journal of Peptide Research 2000, 56(5).
Abstract: Lactoferricins are a class of antibacterial peptides isolated after gastric-pepsin digest of the mammalian iron-chelating-protein lactoferrin. For investigation of antibacterial activity, we prepared short synthetic derivatives of bovine, human, caprine, murine and porcine lactoferricins with 15-amino-acid residues of high sequence homology. The peptides corresponded to amino-acid residues 17ľ31 of the mature bovine lactoferrin. Only the bovine and caprine derivatives displayed measurable antibacterial activity, with the bovine one having a minimal inhibitory concentration of 24 Ám and being 10 times more active than the caprine one against Escherichia coli. An alanine-scan of the bovine lactoferricin derivative was performed to identify specific amino acids that were important for the antibacterial activity. We found that neither of the two tryptophan residues (Trp 6 and Trp 8) present in the bovine lactoferricin derivative could be replaced by alanine without a major loss of antibacterial activity. The other lactoferricin derivatives tested contained only one tryptophan residue (Trp 6). Modified human, caprine and porcine lactoferricin derivatives containing two tryptophan residues (Trp 6 and Trp 8) displayed minimal inhibitory concentrations of 74, 174 and 219 Ám, respectively, which represented up to a six-fold increase in antibacterial activity. The alanine-scan also revealed that the antibacterial activity was increased when acetamidomethyl-protected cysteine and unprotected glutamine (Cys 3 and Gln 7) were replaced with alanine. Only the bovine lactoferricin derivative and a few of its alanine-modified derivatives displayed measurable activity against Staphylococcus aureus.
Keywords: alanine-scan; Antibacterial peptide; Lactoferricin; minimal inhibitory concentration; peptide modifications
Citation: 9

Bulky aromatic amino acids increase the antibacterial activity of 15-residue bovine lactoferricin derivatives

Cited Entries: LFB0031, LFB0053, LFB0054, LFB0055, LFB0056, LFB0057, LFB0058, LFB0059, LFB0060, LFB0061, LFB0062, LFB0063, LFB0064, LFB0065, LFB0066, LFB0067, LFB0068, LFB0069, LFB0070, LFB0071

Authors:Haug, B.E., Skar, M.L., Svendsen, J.S.
Journal: Journal of Peptide Science 2001, 7(8).
Abstract: A model peptide, FKCRRWQWRMKKLGA, residues 17-31 of bovine lactoferricin, has been subjected to structure-antibacterial activity relationship studies. The two Trp residues are very important for antibacterial activity, and analogue studies have demonstrated the significance of the size, shape and aromatic character of the side chains. In the current study we have replaced Trp residues in the model peptide with bulky aromatic amino acids to elucidate further the importance of size and shape. The counterproductive Cys residue in position 3 was also replaced by these aromatic amino acids. The largest aromatic amino acids employed resulted in the most active peptides. The peptides containing these hydrophobic residues were generally more active against Staphylococcus aureus than against Escherichia coli, indicating that the bacterial specificity as well as the antibacterial efficiency can be altered by employing large hydrophobic aromatic amino acid residues.
Keywords: Antibacterial peptide; unnatural aromatic amino acid; bovine lactoferricin; tryptophan
Citation: 10

The role of tryptophan in the antibacterial activity of a 15-residue bovine lactoferricin peptide

Cited Entries: LFB0031, LFB0072, LFB0073, LFB0074, LFB0075, LFB0076, LFB0077, LFB0078, LFB0079, LFB0080, LFB0081, LFB0082, LFB0083

Authors:Haug, B.E., Svendsen, J.S.
Journal: Journal of Peptide Science 2001, 7(4).
CrossRef External Link
Abstract: Bovine lactoferricin is a 25-residue antibacterial peptide isolated after gastric cleavage of the iron transporting protein lactoferrin. A 15-residue fragment, FKCRRWQWRMKKLGA of this peptide sustains most of the antibacterial activity. In this truncated sequence, the two Trp residues are found to be essential for antibacterial activity. The anchoring properties of Trp, as have been observed in membrane proteins, are believed to be important for the interaction of Trp containing antibacterial peptides with bacterial cell membranes. We have investigated the molecular properties which make Trp important for the antibacterial activity of the 15-residue peptide by replacing Trp with natural and unnatural aromatic amino acids. This series of peptides was tested for antibacterial activity against Echerichia coli and Staphylococcus aureus. We found that neither the hydrogen bonding ability nor the amphipathicity of the indole system are essential properties for the effect of Trp on the antibacterial activity of the peptides. Replacement of Trp with residues containing aromatic hydrocarbon side chains gave the most active peptides. We propose that aromatic hydrocarbon residues are able to position themselves deeper into the bacterial cell membrane, making the peptide more efficient in disrupting the bacterial cell membrane. From our results the size, shape and aromatic character of Trp seem to be the most important features for the activity of this class of Trp containing antibacterial peptides.
Keywords: Antibacterial peptide; Lactoferricin; tryptophan; unnatural aromatic amino acids
Citation: 11

Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity

Cited Entries: LFH0002, LFH0003, LFH0016, LFH0017, LFH0018, LFH0019, LFH0020, LFH0056, LFH0080, LFH0081, LFH0082, LFH0083, LFH0084, LFB0031, LFB0041, LFB0046, LFB0097

Authors:Farnaud, S., Spiller, C., Moriarty, L.C., Patel, A., Gant, V., Odell, E.W., Evans, R.W.
Journal: FEMS Microbiology Letters 2004, 233(2).
Keywords: Lactoferrin; Lactoferricin; Cationic antimicrobial peptides; Lps; Mbc
Citation: 12

The antimicrobial peptides lactoferricin B and magainin 2 cross over the bacterial cytoplasmic membrane and reside in the cytoplasm

Cited Entries: LFB0031, LFB0032, LFB0033, LFB0084

Authors:Haukland, H.H., Ulvatne, H., Sandvik, K., Vorland, L.H.
Journal: FEBS Letters 2001, 508(3).
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Keywords: antimicrobial peptide; Lactoferricin; Magainin; Cecropin; Cytoplasmic membrane; Cytoplasm
Citation: 13

The effects of charge and lipophilicity on the antibacterial activity of undecapeptides derived from bovine lactoferricin

Cited Entries: LFB0020, LFB0021, LFB0022, LFB0023, LFB0024, LFB0025, LFB0026, LFB0027, LFB0028, LFB0029, LFB0031

Authors:Str°m, M.B., Rekdal, O., Svendsen, J.S.
Journal: Journal of Peptide Science 2002, 8(1).
Keywords: Antibacterial peptides; bovine lactoferricin; minimal inhibitory concentration; tryptophan; short peptides
Citation: 14

Antibacterial effects of lactoferricin B

Cited Entries: LFB0031, LFB0032, LFB0033, LFB0084

Authors:Vorland, L.H., Ulvatne, H., Andersen, J., Haukland, H.H., Rekdal, O., Svendsen, J.S., Gutteberg, T.J.
Journal: Scandinavian Journal of Infectious Diseases 1999, 31.
Abstract: The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the inhibitory efficacy of lactoferricin of bovine origin (Lf-cin B) on Escherichia coli, Proteus mirabilis and Staphylococcus aureus with or without a cell wall. We found that spheroplasts and protoplasts had a lower MIC than their counterparts with a cell wall. We also compared the efficacies of Lf-cin B (17-31) made of all L-amino acids and all D-amino acids. The peptide made of all D-amino acids was more active than the corresponding L-enantiomer. Furthermore, we examined the influence of Lf-cin B on the motility of E. coli and the influence of temperature on the susceptibility of bacteria exposed to Lf-cin B. Bacteria exposed to sub-MIC of Lf-cin B lost their motility. Bacteria exposed to Lf-cin B at 20 degrees C were more sensitive to Lf-cin B than when exposed at 37 degrees C. These findings indicate that the cell envelope is a limiting step for Lf-cin B to exert its antibiotic effect. We cannot rule out a receptor-mediated first step for Lf-cin B (17-31).
Keywords: PEPTIDE antibiotics; ANTIBACTERIAL agents
Citation: 15

Activity and mode of action against fungal phytopathogens of bovine lactoferricin-derived peptides

Cited Entries: LFB0031, LFB0097

Authors:Munoz, A., Marcos, J.F.
Journal: Journal of Applied Microbiology 2006, 101(6): 1199-1207.
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Abstract: AIM: To evaluate the activity against fungal phytopathogens of two synthetic peptides derived from the protein bovine lactoferricin: the antibacterial active core of six amino acid residues (LfcinB(20-25)) and an extension of 15 amino acids (LfcinB(17-31)). METHODS AND RESULTS: In vitro activity against fungal pathogens was determined and compared with that against model micro-organisms. Activity was demonstrated against fungi of agronomic relevance. Distinct antimicrobial properties in vitro were found for the two peptides. LfcinB(17-31) had growth inhibitory activity higher than LfcinB(20-25). However, LfcinB(17-31) was not fungicidal to quiescent conidia of Penicillium digitatum at the concentrations assayed, while LfcinB(20-25) killed conidia more efficiently. Microscopical observations showed that the mycelium of P. digitatum treated with LfcinB(17-31) developed alterations of growth, sporulation and chitin deposition, and permeation of hyphal cells. In experimental inoculations of mandarins, both peptides showed limited protective effect against the disease caused by P. digitatum. CONCLUSIONS: LfcinB(20-25) and LfcinB(17-31) peptides were shown to have antimicrobial activity against plant pathogenic filamentous fungi, with distinct properties and mode of action. SIGNIFICANCE AND IMPACT OF THE STUDY: LfcinB(20-25) and LfcinB(17-31) peptides offer novel alternatives to develop resistant plants by molecular breeding.
Keywords: Animals; Cattle; Citrus/microbiology; Lactoferrin/*pharmacology; Microbial Sensitivity Tests; Penicillium/*drug effects/ultrastructure; Peptide Fragments/*pharmacology; Plant Diseases/microbiology; Plants/*microbiology
Citation: 16

Prediction of antibiotic activity and synthesis of new pentadecapeptides based on lactoferricins

Cited Entries: LFB0031, LFB0034, LFB0035, LFB0036, LFB0037, LFB0038, LFB0039, LFB0040, LFB0041, LFB0042, LFB0043, LFB0044, LFB0045, LFB0046, LFB0047, LFB0048, LFB0049, LFB0050, LFB0051, LFB0052, LFB0168, LFB0169, LFB0170, LFB0171, LFB0172, LFM0001, LFM0002, LFM0003, LFM0004, LFM0005, LFM0006, LFM0007, LFM0008, LFM0009, LFM0010, LFM0011, LFM0012, LFM0013, LFM0014, LFM0015, LFM0016, LFM0017, LFM0018, LFM0019, LFH0022, LFH0023, LFH0089, LAG0002, LAG0003, LFP0001, LFP0002

Authors:Lejon, T., Stiberg, T., Str°m, M. B., Svendsen, J. S.
Journal: Journal of Peptide Science 2004, 10(6): 6.
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Abstract: The antibacterial activity against Escherichia coli and Staphylococcus aureus has been studied for a number of modified pentadecapeptides based on lactoferricins of different origin. The peptides were classified by multivariate methods and quantitative structureľactivity relationships (QSAR) were developed using theoretically derived variables for the amino acids. For the modified peptides based on bovine lactoferricin (LFB) a model was calculated and used for prediction of new peptides that were then tested for antibacterial activity in order to improve peptide activity and to check the validity of the model. Models were also calculated including lactoferricins of different origin. Theories of the mechanism of action of the peptides are briefly discussed.
Keywords: lactoferrin; lactoferricin; pentadecapeptides; antibacterial activity; QSAR; predictions
Citation: 17

Antibiotic activity of pentadecapeptides modelled from amino acid descriptors

Cited Entries: LFB0031, LFM0001, LFM0002, LFM0003, LFM0004, LFM0005, LFM0006, LFM0007, LFM0008, LFM0009, LFM0010, LFM0011, LFM0012, LFM0013, LFM0014, LFM0015, LFM0016, LFM0017, LFM0018, LFM0019

Authors:Lejon, T., Str°m, M. B., Svendsen, J. S.
Journal: Journal of Peptide Science 2001, 7(2): 7.
Abstract: Pentadecapeptides based on modified murine lactoferricin (LFM) sequences show varying degrees of antibacterial activity against Escherichia coli and Staphylococcus aureus. By means of projections to latent structures (PLS), a good correlation is obtained if the biological activity is modelled as a function of variables describing peptide properties, e.g. a-helicity, hydrophobicity:hydrophilicity and charge. Using variables derived from a principal component analysis (PCA) of all naturally occurring amino acids, it is possible to describe the amino acid content of the peptides using three variables per amino acid position. The resulting descriptor matrix is then used to develop quantitative structureľactivity relationships (QSAR). It is shown that the theoretically derived descriptors model the activity of the peptides better than the earlier model, and that properties of the peptides other than antibacterial activity can be predicted.
Keywords: pentadecapeptides; antibacterial activity; amino acids; antibiotic activity

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