LF f(18-40) modified [id=LFH0024]

Synonym: LF f(18-40) linear ; Lfpep

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

Gram-positive: Staphylococcus aureus (MIC=11 然), Staphylococcus haemolyticus (MIC=45 然), Kocuria rosea ATCC 186 (MIC=6 然).

Gram-negative: Pseudomonas aeruginosa (MIC=45 然), Salmonella typhimurium (MIC=23 然), Escherichia coli ML-35 (MIC=23 然), Escherichia coli IID861 (MIC=18 然 or MIC=50 然)), Escherichia coli O111 (MIC=90 然).

Yeast: Candida albicans ATCC 10231 (MIC=18.7 然), Candida glabrata (MIC=9.3 然), Candida guilliermondii (MIC=9.3 然), Candida krusei (MIC=4.7 然), Candida parapsilosis (MIC=9.3 然), Candida tropicalis (MIC=9.3 然).

Parasite: Giardia lamblia (LD50=5.4 然).

NOTE: No activity against Morganella morganii, Streptococcus mitis (>90 然) .

Description :
Production method: Synthetic.

Peptide with blocked cysteines
The antibacterial properties of the synthetic peptides further confirm that the disulfide bond responsible for the looped structure of the identified domain is not essential for activity (Citation: 5).
Length : 23 Mass (Da): 2 820.11 Common Amino Acids : R
Isolectric Point : 12.1 Net Charge : 7 Absent Amino Acids : ADEHLY
Basic Residues : 7 Acidic Residues : 0 Hydrophobic Residues : 5
Polar Residues : 6 Boman Index : -75.86 Hydropathy Index : -1.026
Aliphatic Index : 42.17 Instability Index : 0 Extinction Coefficient : 5625
Absorbance 280nm : 255.68

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)

 2 LFH0016  100.0%  -----------------TKCFQWQRN----------------------- 
 3 LFH0020   88.9%  -----------------TKCFQWQGN----------------------- 
 4 LFH0017   88.9%  -----------------TKCGQWQRN----------------------- 
 5 LFH0018   77.8%  -----------------TKCFGWGRN----------------------- 
 6 LFH0019   88.9%  -----------------TGCFQWQRN----------------------- 
 7 LFH0011  100.0%  -------------QPEATKCFQWQRNMRKVR------------------ 
 8 LFH0012  100.0%  --------------PEATKCFQWQRNMRKVR------------------ 
 9 LFH0013  100.0%  ---------------EATKCFQWQRNMRKVR------------------ 
10 LFH0014  100.0%  ----------------ATKCFQWQRNMRKVR------------------ 
11 LFH0041   91.7%  -------------------CFQWQRNMRKVA------------------ 
12 LFH0043  100.0%  --------------------FQWQRNMRK-------------------- 
13 LFH0040   91.7%  -------------------CFQWQRNMRKAR------------------ 
14 LFH0015  100.0%  -----------------TKCFQWQRNMRKVR------------------ 
15 LFH0038   91.7%  -------------------CFQWQRNMAKVR------------------ 
16 LFH0039   91.7%  -------------------CFQWQRNMRAVR------------------ 
17 LFH0021  100.0%  -----------------TKCFQWQRNMRKVR------------------ 
18 LFH0027  100.0%  ------------------KCFQWQRNMRKVR------------------ 
19 LFH0030   91.7%  -------------------AFQWQRNMRKVR------------------ 
20 LFH0044  100.0%  --------------------FQWQRNMRKV------------------- 
21 LFH0049  100.0%  --------------------FQWQRNMRKVR------------------ 
22 LFH0045  100.0%  --------------------FQWQRNMRKVR------------------ 
23 LFH0031   91.7%  -------------------CAQWQRNMRKVR------------------ 
24 LFH0055  100.0%  ---------------------QWQRNMRKVR------------------ 
25 LFH0022  100.0%  -----------------TKCFQWQRNMRKVRG----------------- 
26 LFH0029  100.0%  -------------------CFQWQRNMRKVR------------------ 
27 LFH0033   91.7%  -------------------CFQAQRNMRKVR------------------ 
28 LFH0056  100.0%  ------------------------RNMRKVR------------------ 
29 LFH0032   91.7%  -------------------CFAWQRNMRKVR------------------ 
30 LFH0034   91.7%  -------------------CFQWARNMRKVR------------------ 
31 LFH0023   93.3%  -----------------TKCFQWQWNMRKVRG----------------- 
32 LFH0057  100.0%  ---------------------------RKVR------------------ 
33 LFH0035   91.7%  -------------------CFQWQANMRKVR------------------ 
34 LFH0036   91.7%  -------------------CFQWQRAMRKVR------------------ 
35 LFH0046   90.9%  --------------------FQWQRNIRKVR------------------ 
36 LFH0047   90.9%  --------------------FQWQRNIRKVR------------------ 
37 LFH0048   90.9%  --------------------FQWQRNPRKVR------------------ 
38 LFH0037   91.7%  -------------------CFQWQRNARKVR------------------ 
39 LFH0024  100.0%  -----------------TKCFQWQRNMRKVRGPPVSCIKR--------- 
40 LFH0026  100.0%  -----------------TKCFQWQRNMRKVRGPPVSCIKRDS------- 
41 LFH0025  100.0%  -----------------TKCFQWQRNMRKVRGPPVSCIKRDS------- 
42 LFH0042  100.0%  -------------------CFQWQRNMRKVRGPPVSCI----------- 
43 LFH0054  100.0%  --------------------FQWQRNMRKVRGPPVS------------- 
44 LFH0028  100.0%  ------------------KCFQWQRNMRKVRGPPVSCI----------- 
46 LFH0058  100.0%  ---------------------------RKVRGPPVSCIKRDSP------ 
47 LFH0059  100.0%  ------------------------------------CIKRDSP------ 
48 LFH0009A 100.0%  GRRRRSVQWCA-------------------------------------- 
51 LFH0004  100.0%  GRRRRSVQWCA-------------------------------------- 
52 LFH0003  100.0%  GRRRRSVQW---------------------------------------- 
53 LFH0002  100.0%  GRRRRS------------------------------------------- 

Citation: 1

Lactoferricin derived from milk protein lactoferrin

Cited Entries: LFH0024

Authors:Wakabayashi, H., Takase, M., Tomita, M.
Journal: Current Pharmaceutical Design 2003, 9.
Abstract: Lactoferricin (LFcin) was initially identified as an antimicrobial peptide derived by pepsin digestion of lactoferrin (LF), a multifunctional innate-defense protein in milk. Various synthetic analogs of LFcin have also been reported. LFcin inhibits a diverse range of microorganisms such as gram-negative bacteria, gram-positive bacteria, yeast, filamentous fungi, and parasitic protozoa, including some antibiotic-resistant pathogens. LFcin kills target organisms by membrane perturbation and acts synergistically with some antimicrobial agents. LFcin exhibits numerous biological activities in common with those of LF. Whereas LFcin suppresses the activation of innate immunity by microbial components such as lipopolysaccharide (LPS) and CpG DNA, the peptide itself activates immunity. Administration of LFcin analogs has been shown to protect the host via direct antimicrobial activity and immunostimulatory effects in several infection models of mice. Here we present a comprehensive review of investigations of LFcin and related peptides.
Keywords: PEPTIDE antibiotics; Lactoferrin; milk proteins; antimicrobial; immunomodulation; Lactoferricin; lfcin; Milk; multifunctional; Peptide
Citation: 2

Giardicidal activity of lactoferrin and N-terminal peptides

Cited Entries: LFH0024, LFB0084

Authors:Turchany, J.M., Aley, S.B., Gillin, F.D.
Journal: Infection and Immunity 1995, 63(11).
Abstract: Human and bovine lactoferrins and their derived N-terminal peptides were giardicidal in vitro. Fe3+, but not Fe2+, protected trophozoites from both native lactoferrin and peptides, although the latter lack iron-binding sites. Other divalent metal ions protected only against native lactoferrin. Log-phase cells were more resistant to killing than stationary-phase cells. These studies suggest that lactoferrin, especially in the form of the N-terminal peptides, may be an important nonimmune component of host mucosal defenses against Giardia lamblia.
Citation: 3

Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans

Cited Entries: LFH0024

Authors:Wakabayashi, H., Takakura, N., Teraguchi, S., Tamura, Y.
Journal: Microbiol Immunol 2003, 47.
Abstract: Oral administration of lactoferrin (LF), an innate-defense protein present in exocrine secretions such as milk and in neutrophils, is reported to improve host-protection against infections with microorganisms including pathogenic fungi, possibly due to an immunomodulatory effect. This study aimed to evaluate the effect of bovine LF feeding on peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Time course analysis during the 14 days following Candida-priming revealed that LF administration slightly increased the number of peritoneal exudate cells, and significantly enhanced the production of superoxide anion (O2(-)) and nitric oxide (NO) by peritoneal macrophages at day 7. LF administration facilitated NO production and Candida hyphal-growth inhibition by macrophages derived from Candida-primed mice but not non-primed mice, suggesting that the action of LF is dependent on the immune status of the host. LF administration altered the kinetics of cytokines in the peritoneal lavage fluid of Candida-primed mice. Enhancement of cytokine levels by LF was observed for IL-12 at day 5 and IFN-gamma at day 9, but not for TNF-alpha or IL-10. In conclusion, LF feeding augmented the activities of macrophages in a manner dependent on Candida-priming and these effects may be related to enhanced cytokine levels.
Citation: 4

Different anti-candida activities of two human lactoferrin-derived peptides, Lfpep and Kaliocin-1

Cited Entries: LFH0024, LFH0060

Authors:Viejo-Diaz, M., Andres, M.T., Fierro, J.F.
Journal: Antimicrobial Agents and Chemotherapy 2005, 49(7).
Abstract: The synthetic peptides Lfpep and kaliocin-1 include the sequences from positions 18 to 40 and 153 to 183 of human lactoferrin, respectively. Lfpep is a cationic peptide with bactericidal and giardicidal effects, whereas kaliocin-1 is a novel bactericidal peptide that corresponds to a highly homologous sequence present in the transferrin family of proteins. Both peptides presented fungicidal activity against Candida spp., including fluconazole- and amphotericin B-resistant clinical isolates. Lfpep exhibited higher antifungal activity (8- to 30-fold) and salt resistance than kaliocin-1. The killing activity of Lfpep was mediated by its permeabilizing activity on Candida albicans cells, whereas kaliocin-1 was unable to disrupt the cytoplasmic membrane, as indicated by its inability to allow permeation of propidium iodide and the small amount of K+ released. The amino acid sequence of kaliocin-1 includes the "multidimensional antimicrobial signature" conserved in disulfide-containing antimicrobial peptides and a striking similarity to brevinin-1Sa, an antimicrobial peptide from frog skin secretions, exhibiting a "Rana box"-like sequence. These features may be of interest in the design of new antifungals.
Citation: 5

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: 6

Potassium efflux induced by a new lactoferrin-derived peptide mimicking the effect of native human lactoferrin on the bacterial cytoplasmic membrane

Cited Entries: LFH0009, LFH0024, LFH0060

Authors:Viejo-Diaz, M., Andres, M.T., Perez-Gil, J., Sanchez, M., Fierro, J.F.
Journal: Biochemistry (Moscow) 2003, 68(2).
CrossRef External Link
Abstract: A 31-amino acid synthetic peptide (NH2-FFSASCVPGADKGQFPNLCRLCAGTGENKCA-COOH) was chemically synthesized based on the amino acid sequence of a region of human lactoferrin homologous to other sequences present in the N- and C-lobes of all members of the transferrin family proteins. The peptide, termed kaliocin-1, and lactoferrin showed a bactericidal effect in assays performed in low-ionic-strength conditions. This is the first time that it is shown that the antimicrobial effect of lactoferrin depends on the extracellular cation concentration. The antimicrobial effect of kaliocin-1 was lower than that of human lactoferrin, but their activities were inhibited by Na+ or K+ in a cation concentration-dependent manner. In addition, the peptide was able to mimic native lactoferrin, inducing K+-efflux and a selective dissipation of the transmembrane electrical potential of Escherichia coli cells without causing extensive damage to the outer and inner bacterial membranes. In contrast, the peptide, but not lactoferrin, was able to permeabilize different ions through liposomal membranes. The hypothetical interaction of kaliocin-1 with a bacterial membrane compound is discussed based in the different ion flux induced on cellular and artificial membranes as well as data from circular dichroism assays. Kaliocin-1 was not cytotoxic and could be a suitable model for the design of analogs able to mimic the antibacterial effect of human lactoferrin.
Keywords: antimicrobial peptide - lactoferrin-derived peptide - lactoferrin - transferrin - lactoferricin - kaliocin - electrical potential - membrane permeabilization
Citation: 7

Permeabilizing action of an antimicrobial lactoferricin-derived peptide on bacterial and artificial membranes

Cited Entries: LFH0024

Authors:Aguilera, O., Ostolaza, H., Quiros, L.M., Fierro, J.F.
Journal: FEBS Letters 1999, 462(3).
CrossRef External Link
Keywords: Lactoferricin; Lactoferrin; Liposome; antimicrobial peptide; Escherichia coli
Citation: 8

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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