Crimson Publishers Publish With Us Reprints e-Books Video articles


Cohesive Journal of Microbiology & Infectious Disease

Structure-Activity Relationship Study of Synthetic Variants Derived from the Highly Potent Human Antimicrobial Peptide hLF(1-11)

  • Open or Close Carlo PJM Brouwer1,2,3*, Luca Roscini4, Gianluigi Cardinali4,5, Laura Corte4, Debora Casagrande Pierantoni4, Vincent Robert1,3, Mahfuzur Rahman2 and Mick M Welling6

    1Westerdijk, Fungal Biodiversity Institute, Netherlands

    2CBMR Scientific Inc, Canada

    3BioAware Life Sciences Data Management Software, Belgium

    4Department of Pharmaceutical sciences, University of Perugia, Italy

    3CEMIN Research Centre of Excellence, University of Perugia, Italy

    4Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Netherlands

    *Corresponding author: Carlo PJM Brouwer, Westerdijk, Fungal Biodiversity Institute, Uppsalalaan 8, Utrecht 3584 CT, Netherlands, CBMR Scientific Inc., Edmonton, Alberta, Canada, BioAware Life Sciences Data Management Software, Rue du Henrifontaine 20, B-4280 Hannut, Belgium, Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, Utrecht 3584 CT, Netherlands

Submission: January 31, 2018; Published: March 13, 2018

DOI: 10.31031/CJMI.2018.01.000512

ISSN: 2578-0190
Volume1 Issue3


Antimicrobial peptides are omnipresent in nature and act as the first line of defence of the host against infectious agents. A synthetic antimicrobial peptide derived from the N-terminus of human lactoferrin hLF(1-11) (GRRRRSVQWCA), displays antibacterial as well as antifungal activity in vitro and in vivo. In order to elucidate the mechanism of antimicrobial action of hLF(1-11), we have synthesised several peptides analogues derived from hLF(1- 11) to test their activity against various fungal and bacterial strains. In this way, a general trend on the importance of the order and position of amino acid residues for biological activity against various organisms could be drawn.

In this study, the full Ala-scan has been synthesised (i.e. series of structural variants where a different residue is replaced with an alanine residue); the affinity of the analogue peptide was assessed and compared with that of the original. Additionally, we performed combination therapy with hLF(1-1) peptides and classical antibiotics as this may serve as an alternative approach to improve antimicrobial treatment outcome in drug resistant strains. The biological tests showed a decrease in the activity of the peptide when one out of the first three arginine residues, the tryptophan or the cysteine residue were replaced by alanine. Replacement of the cysteine residue by a serine residue or by a methylated cysteine led to peptides that were significantly less potent than the reference peptide hLF(1 11). However, the peptide containing a cysteine residue; the disulphide dimer showed the same activity as the monomer. Finally, it was also possible to replace the tryptophan residue by another aromatic residue phenylalanine without any loss of activity. Amidation of the C-terminus did not negatively affect the biological activity of the peptide but even increased, while acetylation of the N-terminus led to a significant loss of antimicrobial activity. The synthesis of analogues from hLF(1 11) and their use in biological tests revealed the importance of some amino acid residues for antimicrobial activity; that are arginine (position 2), tryptophan (position 9) and cysteine (position 10). Secondly, in combination with classical antibiotics even for the drug resistant species we found synergistic interactions between the peptide and antibiotics in vivo. In conclusion, some amino acid sequences/places of hLF(1-11)are important for the antimicrobial actions and in synergistic processes.

Keywords: AMP; Biological activity; Synergism; Fungal infections

Get access to the full text of this article

About Crimson

We at Crimson Publishing are a group of people with a combined passion for science and research, who wants to bring to the world a unified platform where all scientific know-how is available read more...

Leave a comment

Contact Info

  • Crimson Publishers, LLC
  • 555 Madison Avenue, 5th floor
  •     New York, NY 10022, USA
  • +1 (929) 600-8049
  • +1 (929) 447-1137