The effects of charge and lipophilicity on the antibacterial activity of undecapeptides derived from bovine lactoferricin

Peptides derived from human and bovine lactoferricin were designed, synthesized, purified, and characterized using RP-HPLC and MALDI-TOF-MS. Specific changes in the sequences were designed as (i) the incorporation of unnatural amino acids in the sequence, the (ii) reduction or (iii) elongation of the peptide chain length, and (iv) synthesis of molecules with different number of branches containing the same sequence. For each peptide, the antibacterial activity againstEscherichia coliATCC 25922 andEnterococcus faecalisATCC 29212 was evaluated. Our results showed that Peptides I.2 (RWQWRWQWR) and I.4 ((RRWQWR)4K2Ahx2C2) exhibit bigger or similar activity againstE. coli(MIC 4–33 μM) andE. faecalis(MIC 10–33 μM) when they were compared with lactoferricin protein (LF) and some of its derivate peptides as II.1 (FKCRRWQWRMKKLGA) and IV.1 (FKCRRWQWRMKKLGAPSITCVRRAE). It should be pointed out that Peptides I.2 and I.4, containing the RWQWR motif, are short and easy to synthesize; our results demonstrate that it is possible to design and obtain synthetic peptides that exhibit enhanced antibacterial activity using a methodology that is fast and low-cost and that allows obtaining products with a high degree of purity and high yield.

Download Full-text

Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens

BioMed Research International ◽

10.1155/2018/5252891 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Sandra C. Vega Chaparro ◽

J. Tatiana Valencia Salguero ◽

Diana A. Martínez Baquero ◽

Jaiver E. Rosas Pérez

Keyword(s):

Antibacterial Activity ◽

High Performance ◽

Solid Phase ◽

Solid Phase Peptide Synthesis ◽

Therapeutic Agents ◽

Ionization Time ◽

Gram Positive Bacteria ◽

Flight Mass Spectrometry ◽

Bovine Lactoferricin ◽

Healthcare Associated

Antimicrobial peptides (AMPs) are gaining interest as potential therapeutic agents. Peptides derived from bovine lactoferricin B (LfcinB) have been reported to exhibit antimicrobial activity, and the LfcinB RRWQWR sequence is the smallest known motif that exhibits antibacterial and cytotoxic activity. Our goal was to examine the effect of multicopy arrangements of the RRWQWR motif, on its antibacterial activity against healthcare-associated infections (HCAIs). Linear and branched peptides containing the RRWQWR motif were generated using solid phase peptide synthesis-Fmoc/tBu methodology, purified, and characterized using reverse phase-high performance liquid chromatography and matrix-assisted laser desorption/ionization time of flight mass spectrometry. For each peptide, the antibacterial activity againstStaphylococcus aureus(ATCC 25923 and 33591 strains) andKlebsiella pneumoniae(ATCC 13883 and 700603 strains) was assessed by measuring the minimum inhibitory and the minimum bactericidal concentrations, in the exponential phase. Cells were observed by scanning electron microscopy, and the hemolytic activity of the peptides was assessed. The overall results demonstrate that, compared to linear analogues, polyvalent presentation of the RRWQWR motif enhances its antibacterial activity against both Gram-negative and Gram-positive bacteria even on resistant strain.

Download Full-text