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Lactoferricin M [id=LFM0001]

Synonym: LF f(16-30)

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

Gram-positive: Staphylococcus aureus ATCC 25923 (MIC=500 然 or MIC>500 然).

Gram-negative: Escherichia coli ATCC 25922 (MIC=500 然 or MIC>500 然).

Description :
Production method: Synthetic.

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 1).
Length : 15 Mass (Da): 1 834.53 Common Amino Acids : GKER
Isolectric Point : 9.67 Net Charge : 2 Absent Amino Acids : ADFHIPSTY
Basic Residues : 4 Acidic Residues : 2 Hydrophobic Residues : 3
Polar Residues : 4 Boman Index : -49.94 Hydropathy Index : -1.34
Aliphatic Index : 45.33 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 LFM0020 100.0%  EKCLRWQNEMRKVGGPPLSCVKKSS 
 2 LFM0013  80.0%  EKCLRWQWAMRKYGG---------- 
 3 LFM0016  80.0%  EKCLRWQWRMRKYGG---------- 
 4 LFM0018  73.3%  RKCLRWQWAMRKYGG---------- 
 5 LFM0019  73.3%  RKCLRWQWRMRKYGG---------- 
 6 LFM0003  86.7%  EKCLRWQWEMRKYGG---------- 
 7 LFM0015  80.0%  RKCLRWQWEMRKYGG---------- 
 8 LFM0012  80.0%  AKCLRWQWEMRKYGG---------- 
 9 LFM0014  73.3%  AKCLRWQWAMRKYGG---------- 
10 LFM0017  73.3%  AKCLRWQWRMRKYGG---------- 
11 LFM0005  86.7%  EKCLRWQWAMRKVGG---------- 
12 LFM0008  86.7%  EKCLRWQWRMRKVGG---------- 
13 LFM0010  80.0%  RKCLRWQWAMRKVGG---------- 
14 LFM0011  80.0%  RKCLRWQWRMRKVGG---------- 
15 LFM0006  80.0%  AKCLRWQWAMRKVGG---------- 
16 LFM0009  80.0%  AKCLRWQWRMRKVGG---------- 
17 LFM0004  86.7%  AKCLRWQWEMRKVGG---------- 
18 LFM0007  86.7%  RKCLRWQWEMRKVGG---------- 
19 LFM0021 100.0%  ---LRWQNEMRKV------------ 
20 LFM0001 100.0%  EKCLRWQNEMRKVGG---------- 
21 LFM0002  93.3%  EKCLRWQWEMRKVGG---------- 

Citation: 1

Increased antibacterial activity of 15-residue murine lactoferricin derivatives

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

Authors:Str鷰, M.B., Stensen, W., Svendsen, J.S., Rekdal, O.
Journal: The Journal of Peptide Research 2001, 57(2).
Abstract: LFM W8 is a synthetic 15-residue lactoferricin derivative (H2N-EKCLRWQWEMRKVGG-COOH), corresponding to residues 16-30 of the mature murine lactoferrin protein except that the asparagine residue in position 8 of the native peptide is replaced with tryptophan. We have previously reported that the two tryptophan residues in positions 6 and 8 are of crucial importance for the antibacterial activity of many lactoferricin derivatives but, despite fulfilling this requirement, LFM W8 is inactive against Escherichia coli and Staphylococcus aureus. In order to solve this puzzle, a quantitative structure-antibacterial activity relationship study of synthetic LFM W8 derivatives was performed by replacing the glutamate residues in positions 1 and 9 with arginine or alanine, and the valine residue in position 13 with tyrosine. The results from the study were analyzed using multivariate data analysis. The derived mathematical model clustered the peptides into distinct groups which reflected their antibacterial activities, pointed out correlations between different structural parameters, highlighted the structural parameters that were important for antibacterial activity, and enabled us to predict the activity of a 15-residue bovine lactoferricin derivative. The results showed that net charge and micelle affinity, as determined from the ratio of alpha-helicity in sodium dodecyl sulfate micelles and in 1,1,1,3,3,3-hexafluoro-2-propanol, were the most important structural parameters affecting antibacterial activity. The most active derivative, LFM R1,9 W8 Y13, displayed a minimal inhibitory concentration of 10 and 12 microM against E. coli and S. aureus, respectively. This represented more than 50-fold and 40-fold increases in antibacterial activity, respectively, compared with LFM W8.
Keywords: Antibacterial peptides; minimal inhibitory concentration; murine lactoferricin; peptide modifications; Qsar
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

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.
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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 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
Citation: 4

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鷰, 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 structureactivity 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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