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LF f(1-11) [id=LFH0004]

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

Gram-positive: Staphylococcus aureus 2141 (MIC=18 mM), Listeria monocytogenes EGD (no MIC).

Gram-negative: Klebsiella pneumoniae ATCC 43816 (no MIC), Escherichia coli O54 (no MIC), Acinetobacter baumannii RUH 875 (no MIC), Acinetobacter baumannii LUH 7858 (no MIC), Acinetobacter baumannii RUH 134 (no MIC), Acinetobacter baumannii LUH 7213 (no MIC), Acinetobacter baumannii LUH 6034 (no MIC).

Yeast: Candida albicans Y01-19 (no MIC).

Filamentous fungi: Aspergillus fumigatus (MIC=5 ΅M or EC50=29 ΅M).

Description :
Production method: Synthetic.

Length : 11 Mass (Da): 1 374.94 Common Amino Acids : R
Isolectric Point : 12.5 Net Charge : 4 Absent Amino Acids : DEFHIKLMNPTY
Basic Residues : 4 Acidic Residues : 0 Hydrophobic Residues : 3
Polar Residues : 3 Boman Index : -58.22 Hydropathy Index : -1.373
Aliphatic Index : 35.45 Instability Index : 0 Extinction Coefficient : 5500
Absorbance 280nm : 550

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 LFH0010  100.0%  GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQA 
 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----------- 
45 LFH0007  100.0%  GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCI-- 
46 LFH0058  100.0%  ---------------------------RKVRGPPVSCIKRDSP------ 
47 LFH0059  100.0%  ------------------------------------CIKRDSP------ 
48 LFH0009A 100.0%  GRRRRSVQWCA-------------------------------------- 
49 LFH0009B 100.0%  -----------VSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCI-- 
50 LFH0005  100.0%  GRRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCI-- 
51 LFH0004  100.0%  GRRRRSVQWCA-------------------------------------- 
52 LFH0003  100.0%  GRRRRSVQW---------------------------------------- 
53 LFH0002  100.0%  GRRRRS------------------------------------------- 
54 LFH0006   97.9%  GRRRRSVQWCAVSQPEATKCFQWQRNMRRVRGPPVSCIKRDSPIQCI-- 

Citation: 1

Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria

Cited Entries: LFH0004, LFH0045, LFH0097, LFH0098, LFH0099, LFH0100

Authors:Nibbering, P.H., Ravensbergen, E., Welling, M.M., van Berkel, L.A., van Berkel, P.H.C., Pauwels, E.K.J., Nuijens, J.H.
Journal: Infection and Immunity 2001, 69(3).
Abstract: Since human lactoferrin (hLF) binds to bacterial products through its highly positively charged N terminus, we investigated which of the two cationic domains is involved in its bactericidal activity. The results revealed that hLF lacking the first three residues (hLF[-]3N) was less efficient than hLF in killing of antibiotic-resistant Staphylococcus aureus, Listeria monocytogenes, and Klebsiella pneumoniae. Both hLF preparations failed to kill Escherichia coli O54. In addition, hLF[-]3N was less effective than hLF in reducing the number of viable bacteria in mice infected with antibiotic-resistant S. aureus and K. pneumoniae. Studies with synthetic peptides corresponding to the first 11 N-terminal amino acids, designated hLF(1-11), and fragments thereof demonstrated that peptides lacking the first three N-terminal residues are less effective than hLF(1-11) in killing of bacteria. Furthermore, a peptide corresponding to residues 21 to 31, which comprises the second cationic domain, was less effective than hLF(1-11) in killing of bacteria in vitro and in mice having an infection with antibiotic-resistant S. aureus or K. pneumoniae. Using fluorescent probes, we found that bactericidal hLF peptides, but not nonbactericidal peptides, caused an increase of the membrane permeability. In addition, hLF killed the various bacteria, most probably by inducing intracellular changes in these bacteria without affecting the membrane permeability. Together, hLF and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant S. aureus and K. pneumoniae, and the first two arginines play an essential role in this activity.
Citation: 2

Various routes of administration of 99mTc-labeled synthetic lactoferrin antimicrobial peptide hLF 1-11 enables monitoring and effective killing of multidrug-resistant Staphylococcus aureus infections in mice

Cited Entries: LFH0004

Authors:Brouwer, C.P.J.M., Welling, M.M.
Journal: Peptides 2008, 29(7).
CrossRef External Link
Abstract: The synthetic antimicrobial peptide representative of the first 11 N-terminal amino acids of human lactoferrin (hLF 1–11) kills multidrug-resistant Staphylococcus aureus (MRSA). This study displays antimicrobial activity of hLF 1–11, via various routes of administration, against MRSA infections in mice. Radiolabeling hLF 1–11 with technetium-99m (99mTc-hLF 1–11) enables scintigraphic monitoring directly after administration. 99mTc-hLF 1–11 was taken up by the gall bladder, intestines, and kidneys. Most of the radioactivity was captured in the urinary bladder and about 1% of the injected dose accumulated into infected thigh muscles. At 2 or 24 h after either intravenously, subcutaneously, intraperitoneally, or orally injected a single dose of 0.04 mg/kg hLF 1–11 in mice significantly reduced (20–60 times) the number of viable MRSA. In a dose-response setting in immunocompetent mice maximum bactericidal effects (10,000 times reduction) of intravenously injected 99mTc-hLF 1–11 was seen with 40 mg/kg whereas the same dose of orally administered 99mTc-hLF 1–11 induced about approximately 100 times reduction. In conclusion, intravenously and orally administrated 99mTc-hLF 1–11 accumulates in infected tissues and is highly effective against experimental infections with MRSA. Moreover, scintigraphy is an excellent tool to study the pharmacology of experimental compounds and to determine the uptake in infected tissues.
Keywords: MRSA infection; Lactoferrin peptide; 99mTc-labeling; Routes of administration; Scintigraphy; Antibacterial therapy
Citation: 8

Human antimicrobial peptides’ antifungal activity against Aspergillus fumigatus

Cited Entries: LFH0004

Authors:Lupetti, A., van Dissel, J. T., Brouwer, C. P. J. M., Nibbering, P. H.
Journal: European Journal of Clinical Microbiology & Infectious Diseases 2008, 27: 5.
CrossRef External Link
PubMed link
Abstract: In light of the need for new antifungals, we compared the in vitro antifungal activity of two peptides derived from human lactoferrin (hLF), i.e., hLF(1–11) and hLF(21–31), two analogs of histatin 5, further referred to as dhvar4 and dhvar5, and two ubiquicidin (UBI)-derived peptides, i.e., UBI 18–35 and UBI 29–41, with that of amphotericin B against Aspergillus fumigatus hyphae using the MTT assay. The results revealed a dose-dependent antifungal activity for all peptides, with dhvar5 being the most potent peptide. In addition, hLF(1–11), dhvar5, and UBI 18–35 were effective against A. fumigatus conidia. Furthermore, hLF(1–11) did not lyze human erythrocytes, whereas dhvar5 (≥16 μM) and UBI 18–35 (≥20 μM) were hemolytic. Based on these in vitro results and their effectiveness against infections in mice, we concluded that hLF(1–11) and dhvar5 are promising candidates for the development of new agents against A. fumigatus infections.

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