LF f(17-31) modified [id=LFB0041]

Synonym: LFB A8

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

Gram-negative: Escherichia coli K12 D21e19 (MIC=320 然), Escherichia coli K12 D21e7 (MIC=640 然), Escherichia coli K12 W3110 (MIC=640 然), Escherichia coli K12 D21 (MIC=640 然), Escherichia coli K12 D21f1 (MIC=640 然), Escherichia coli K12 D21f2 (MIC=640 然), Escherichia coli MLK53 (MIC=320 然), Escherichia coli MLK1067 (MIC=320 然), Escherichia coli MLK986 (MIC=320 然), Escherichia coli WA707 (MIC=640 然), Escherichia coli WA834 (MIC=320 然), Escherichia coli ATCC 25922 (MIC=100 然 or MIC>100 然).

Gram-positive: Staphylococcus aureus ATCC 25923 (MIC=100 然 or MIC>100 然).

Description :
Production method: Synthetic.

Eighth residue replaced with alanine.
A series of peptides where each of the residues in LFB was replaced by alanine was prepared and tested for antibacterial activity (LFB0035, LFB0036, LFB0037, LFB0038, LFB0039, LFB0040, LFB0041, LFB0042, LFB0043, LFB0044, LFB0045, LFB0046, LFB0047). The most severe loss of antibacterial activity was observed for derivatives where one of the two tryptophan residues in positions 6 (LFB0039) and 8 (LFB0041) was replaced by alanine (citation: 1).
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: 3).
Length : 15 Mass (Da): 1 879.70 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 : -48.53 Hydropathy Index : -1.027
Aliphatic Index : 39.33 Instability Index : 0 Extinction Coefficient : 5500
Absorbance 280nm : 392.86

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

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; microcalorimКtrie; peptide antimicrobien; rКsonance magnКtique nuclКaire; spectroscopie fluorescence
Citation: 2

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鷰, 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 1731 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 痠 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 痠, 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: 3

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: 4

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鷰, M. B., Svendsen, J. S.
Journal: Journal of Peptide Science 2004, 10(6): 6.
CrossRef External Link
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 structureactivity 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

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