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LF f(15-31) [id=LFH0012]

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

Gram-positive: Active against Enterococcus faecalis ATCC 19433, Staphylococcus epidermidis CCUG 18000A, Staphylococcus aureus CCUG 1800 at 25 µg/ml.

NOTE: No activity against Klebsiella pneumoniae CCUG 9997, Staphylococcus aureus MRS 3526 at 25 µg/ml, Escherichia coli O6K5, Escherichia coli O14, Candida albicans ATCC 64549 at 10 µg/ml .

Description :
Production method: Synthetic.

In order to find an optimal peptide length within the peptide sequence 14–31 (LFH0011) with regard to antimicrobial activity, amino acid residues were removed one by one, starting from the N-terminal end. The most active peptides were the ones corresponding to residues LFH0014, LFH0021, LFH0027, and LFH0030. The trends of increasing antimicrobial activity from sequence 14–31 (LFH0011) to 17–31 (LFH0014) and decreasing from sequence 20–31 (LFH0029) to 22–31 (LFH0055) were statistically significant (Citation : 1).
Length : 17 Mass (Da): 2 179.21 Common Amino Acids : R
Isolectric Point : 11.55 Net Charge : 4 Absent Amino Acids : DGHILSY
Basic Residues : 5 Acidic Residues : 1 Hydrophobic Residues : 4
Polar Residues : 3 Boman Index : -68.17 Hydropathy Index : -1.488
Aliphatic Index : 22.94 Instability Index : 0 Extinction Coefficient : 5500
Absorbance 280nm : 343.75

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

Structure-microbicidal activity relationship of synthetic fragments derived from the antibacterial alpha-helix of human lactoferrin

Cited Entries: LFH0011, LFH0012, LFH0013, LFH0014, LFH0015, LFH0021, LFH0027, LFH0029, LFH0030, LFH0031, LFH0032, LFH0033, LFH0034, LFH0035, LFH0036, LFH0037, LFH0038, LFH0039, LFH0040, LFH0041, LFH0045, LFH0055, LFH0066, LFH0067, LFH0068, LFH0069, LFH0070, LFH0071, LFH0072, LFH0073, LFH0074, LFH0075, LFH0076, LFH0077, LFH0078

Authors:Haversen, L., Kondori, N., Baltzer, L., Hanson, L.A., Dolphin, G.T., Duner, K., Mattsby-Baltzer, I.
Journal: Antimicrobial Agents and Chemotherapy. 2010, 54(1).
Abstract: There is a need for new microbicidal agents with therapeutic potential due to antibiotic resistance in bacteria and fungi. In this study, the structure-microbicidal activity relationship of amino acid residues 14 to 31 (sequence 14-31) from the N-terminal end, corresponding to the antibacterial {alpha}-helix of human lactoferrin (LF), was investigated by downsizing, alanine scanning, and substitution of amino acids. Microbicidal analysis (99% killing) was performed by a microplate assay using Escherichia coli, Staphylococcus aureus, and Candida albicans as test organisms. Starting from the N-terminal end, downsizing of peptide sequence 14-31 showed that the peptide sequence 19-31 (KCFQWQRNMRKVR, HL9) was the optimal length for antimicrobial activity. Furthermore, HL9 bound to lipid A/lipopolysaccharide, as shown by neutralizing endotoxic activity in a Limulus assay. Alanine scanning of peptide sequence 20-31 showed that Cys20, Trp23, Arg28, Lys29, or Arg31 was important for expressing full killing activity, particularly against C. albicans. Substituting the neutral hydrophilic amino acids Gln24 and Asn26 for Lys and Ala (HLopt2), respectively, enhanced microbicidal activity significantly against all test organisms compared to the amino acids natural counterpart, also, in comparison with HL9, HLopt2 had more than 10-fold-stronger fungicidal activity. Furthermore, HLopt2 was less affected by metallic salts than HL9. The microbicidal activity of HLopt2 was slightly reduced only at pH 7.0, as tested in the pH range of 4.5 to 7.5. The results showed that the microbicidal activity of synthetic peptide sequences, based on the antimicrobial {alpha}-helix region of LF, can be significantly enhanced by optimizing the length and substitution of neutral amino acids at specific positions, thus suggesting a sequence lead with therapeutic potential.

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