- Host defense peptide
- Antimicrobial peptides
- Innate immunity
- Structure-activity relationship
- Antibiotic resistance
Fowlicidins are a group of newly identified chicken cathelicidin host defense peptides. We have shown that the putatively mature fowlicidin-2 of 31 amino acid residues possesses potent antibacterial and lipopolysaccharide (LPS)- neutralizing activities, but with a noticeable toxicity to mammalian cells. As a first step in exploring the structure-activity relationships of fowlicidin-2, in this study we determined its tertiary structure by nuclear magnetic resonance spectroscopy. Unlike the majority of cathelicidins, which are composed of a predominant α-helix with a short hinge sequence near the center, fowlicidin-2 consists of 2 well-defined α-helical segments (residues 6–12 and 23–27) connected by a long extensive kink (residues 13–20) induced by proline. To further investigate the functional significance of each of these structural components, several N- and C-terminal deletion analogs of fowlicidin-2 were synthesized and analyzed for their antibacterial, cytotoxic and LPS-neutralizing activities. Our results indicated that neither the N- nor C-terminal α-helix alone is sufficient to confer any function. Rather, fowlicidin-2(1–18) and fowlicidin-2(15–31), 2 α-helical segments with inclusion of the central cationic kink region, retained substantial capacities to kill bacteria and neutralize the LPS-induced proinflammatory response, relative to the parent peptide. More desirably, these 2 peptide analogs showed substantially reduced toxicity to human erythrocytes and epithelial cells, indicative of improved potential as antibacterial and antisepsis agents. To our knowledge, fowlicidin-2 is the first α-helical cathelicidin, with the central kink region shown to be critically important in killing bacteria and neutralizing LPS.
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Dr. Guolong Zhang
Department of Animal Science, Oklahoma State University
212D Animal Science Bldg
Stillwater, OK 74078 (USA)
Tel. +1 405 744 6619, Fax +1 405 744 7390, E-Mail firstname.lastname@example.org
Y.X. and A.H. contributed equally to this paper.
Received: July 17, 2008
Accepted after revision: September 29, 2008
Published online: November 14, 2008
Number of Print Pages : 13
Number of Figures : 7, Number of Tables : 2, Number of References : 35
Journal of Innate Immunity
Vol. 1, No. 3, Year 2009 (Cover Date: April 2009)
Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)
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