LF f(17-41) modified [id=LFB0089]

Synonym: LF f(17-41) linear

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

Gram-positive: Staphylococcus aureus ATCC 25923 (MIC=90 痢/ml), Staphylococcus aureus JCM-2151 (MIC=2 然), Listeria monocytogenes IDF-Ib (MIC=0.3 然), Staphylococcus aureus JCM2151 (MIC=6 然).

Gram-negative: Escherichia coli ATCC 25922 (MIC=90 痢/ml), Escherichia coli IID861 (MIC=2 然 or MIC=6 然), Klebsiella pneumoniae JCM-1662T (MIC=3 然), Pseudomonas aeruginosa IFO-3446 (MIC=3 然).

Description :
Production method: Synthetic.

Peptide with blocked cysteines.
The antibacterial properties of LFB0089 confirm that the disulfide bond responsible for the looped structure of the identified domain is not essential for activity (Citation: 1).
The cyclic bovin lactoferricin (LFB0086) and the linear lactoferricins of bovine (LFB0089), human (LFH0026), murine (LFM0020)and caprine (LAG0006) origin were synthesized and analyzed by mass spectrometry. Only Lf-cinB (LFB0086 and LFB0089) showed significant antibacterial activity against E. coli and S. aureus. We found that cyclic Lf-cin B (LFB0086) was more active than linear Lf-cin B (LFB0089) (Citation: 2).
Length : 25 Mass (Da): 3 126.25 Common Amino Acids : R
Isolectric Point : 12.35 Net Charge : 8 Absent Amino Acids : DEHNY
Basic Residues : 8 Acidic Residues : 0 Hydrophobic Residues : 9
Polar Residues : 5 Boman Index : -68.79 Hydropathy Index : -0.576
Aliphatic Index : 50.8 Instability Index : 0 Extinction Coefficient : 11125
Absorbance 280nm : 463.54

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
  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-----------   


101 LFB0091   100.0%    FKCRRWQWRMKKLGAPSITCVRRAFA------   

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

104 LFB0121   100.0%    ----------------------------CIRA   

Citation: 1

Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin

Cited Entries: LFB0084, LFB0089

Authors:Bellamy, W., Takase, M., Wakabayashi, H., Kawase, K., Tomita, M.
Journal: Journal of Applied Microbiology 1992, 73(6).
Abstract: A physiologically diverse range of Gram-positive and Gram-negative bacteria was found to be susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by gastric pepsin digestion of bovine lactoferrin. The list of susceptible organisms includes Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans, Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium perfringens. Concentrations of lactoferricin B required to cause complete inhibition of growth varied within the range of 0.3 to 150 micrograms/ml, depending on the strain and the culture medium used. The peptide showed activity against E. coli O111 over the range of pH 5.5 to 7.5 and was most effective under slightly alkaline conditions. Its antibacterial effectiveness was reduced in the presence of Na+, K+, Mg2+ or Ca2+ ions, or in the presence of various buffer salts. Lactoferricin B was lethal, causing a rapid loss of colony-forming capability in most of the species tested. Pseudomonas fluorescens, Enterococcus faecalis and Bifidobacterium bifidum strains were highly resistant to this peptide.
Citation: 2

Lactoferricin of bovine origin is more active than lactoferricins of human, murine and caprine origin

Cited Entries: LFH0026, LFB0086, LFB0089, LAG0006, LFM0020

Authors:Vorland, L.H., Ulvatne, H., Andersen, J., Haukland, H.H., Rekdal, ., Svendsen, J.S., Gutteberg, T.J.
Journal: Scandinavian Journal of Infectious Diseases 1998, 30.
Abstract: The antimicrobial peptide lactoferricin is generated by gastric pepsin cleavage of lactoferrin. We have examined the antimicrobial activity of lactoferricins derived from lactoferrin of human, murine, caprine and bovine origin with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against E. coli ATCC 25922 and S. aureus ATCC 25923. We found that lactoferricin of bovine origin (Lf-cin B) was the most efficacious of the lactoferricins tested. By comparing the linear and cyclic Lf-cin B we found the cyclic peptide to be the most active. Lactoferricin B was moderately active against E. coli ATCC 25922 and S. aureus ATCC 25923, but had no activity against P. mirabilis or Y. enterocolitica. Lf-cin B showed good activity against C. albicans, C. tropicalis and C. neoformans.
Keywords: PEPTIDE antibiotics; Lactoferrin
Citation: 3

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: 4

Identification of the bactericidal domain of lactoferrin

Cited Entries: LFH0009, LFH0024, LFB0084, LFB0089

Authors:Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K., Tomita, M.
Journal: Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 1992, 1121(1-2).
CrossRef External Link
Abstract: We report the existence of a previously unknown antimicrobial domain near the N-terminus of lactoferrin in a region distinct from its iron-binding sites. A single active peptide representing this domain was isolated following gastric pepsin cleavage of human lactoferrin, and bovine lactoferrin, and sequenced by automated Edman degradation. The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin. Synthetic analogs of this region similarly exhibited potent antibacterial properties. The active peptide of bovine lactoferrin was more potent than that of human lactoferrin having effectiveness against various Gram-negative and Gram-positive bacteria at concentrations between 0.3 μM and 3.0 μM, depending on the target strain. The effect of the isolated domain was lethal causing a rapid loss of colony-forming capability. Our studies suggest this domain is the structural region responsible for the bactericidal properties of lactoferrin.
Keywords: Lactoferrin; Bactericidal domain; antimicrobial peptide; Lactoferricin
Citation: 5

A review: The active peptide of lactoferrin

Cited Entries: LFH0024, LFB0084, LFB0089, LFB0097, LFB0178, LFB0179

Authors:Tomita, M., Takase, M., Bellamy, W., Shimamura, S.
Journal: Acta Paediatrica Japonica 1994, 36.
Abstract: A potent antimicrobial peptide, lactoferricin, was found to be generated upon gastric pepsin cleavage of lactoferrin. The active peptide consists mainly of a loop of 18 amino acid residues, derived from the N-terminal region of the lactoferrin molecule, Like various other antimicrobial peptides that display membrane-disruptive properties, it contains a high proportion of basic amino acid residues. A physiologically diverse range of micro-organisms was tested and found to be susceptible to inhibition by this natural peptide including Gram-negative and Gram-positive bacteria, yeasts and filamentous fungi. Its antimicrobial effect against sensitive micro-organisms was lethal. Electron microscopy studies revealed that it induces a profound change in cell ultrastructural features and causes substantial cell damage in bacteria and fungi. These findings suggest the possibility that active peptides of lactoferrin may have a role in the host defense against microbial disease. If produced in substantial quantities in vivo such peptides could have important physiological significance, especially in nursing infants.
Keywords: antimicrobial peptide, lactofemcin, lactoferrin, pepsin digestion.

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