tailieunhanh - Báo cáo khoa học: Fowlicidin-3 is an a-helical cationic host defense peptide with potent antibacterial and lipopolysaccharideneutralizing activities

Cathelicidins are an important family of cationic host defense peptides in vertebrates with both antimicrobial and immunomodulatory activities. Fowlicidin-1 and fowlicidin-2 are two newly identified chicken cathelicidins with potent antibacterial activities. Here we report structural and func-tional characterization of the putatively mature form of the third chicken cathelicidin, fowlicidin-3, for exploration of its therapeutic potential. | ễFEBS Journal Fowlicidin-3 is an a-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities Yugendar R. Bommineni1 Huaien Dai2 Yu-Xi Gong2 Jose L. Soulages3 Samodha C. Fernando1 Udaya DeSilva1 Om Prakash2 and Guolong Zhang1 1 Department of AnimalScience Oklahoma State University Stillwater OK USA 2 Department of Biochemistry Kansas State University Manhattan KS USA 3 Department of Biochemistry and Molecular Biology Oklahoma State University Stillwater OK USA Keywords antibiotic resistance antimicrobialpeptide cathelicidin host defense structure-activity relationship Correspondence O. Prakash Department of Biochemistry Kansas State University Manhattan KS 66506 USA Fax 1785 532 7278 Tel 1785 532 2345 E-mail omp@ G. Zhang Department of AnimalScience Oklahoma State University Stillwater OK 74078 USA Fax 1405 744 7390 Tel 1405 744 6619 E-mail zguolon@ These authors contributed equally to this paper Received 13 October 2006 revised 7 November 2006 accepted 10 November 2006 Cathelicidins are an important family of cationic host defense peptides in vertebrates with both antimicrobial and immunomodulatory activities. Fowlicidin-1 and fowlicidin-2 are two newly identified chicken cathelicidins with potent antibacterial activities. Here we report structural and functional characterization of the putatively mature form of the third chicken cathelicidin fowlicidin-3 for exploration of its therapeutic potential. NMR spectroscopy revealed that fowlicidin-3 comprises 27 amino-acid residues and adopts a predominantly a-helical structure extending from residue 9 to 25 with a slight kink induced by a glycine at position 17. It is highly potent against a broad range of Gram-negative and Gram-positive bacteria in vitro including antibiotic-resistant strains with minimum inhibitory concentrations in the range 1-2 pM. It kills bacteria quickly permeabilizing cytoplasmic membranes immediately on coming into contact .