The cyclic cystine ladder in θ-defensins is important for structure and stability, but not antibacterial activity

Conibear, Anne C., Rosengren, K. Johan, Daly, Norelle, Henriques, Sonia Troeira, and Craik, David J. (2013) The cyclic cystine ladder in θ-defensins is important for structure and stability, but not antibacterial activity. Journal of Biological Chemistry, 288 (15). pp. 10830-10840.

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θ-Defensins are ribosomally synthesized cyclic peptides found in the leukocytes of some primate species and have promising applications as antimicrobial agents and scaffolds for peptide drugs. The cyclic cystine ladder motif, comprising a cyclic peptide backbone and three parallel disulfide bonds, is characteristic of θ-defensins. In this study, we explore the role of the cyclic peptide backbone and cystine ladder in the structure, stability, and activity of θ-defensins. θ-Defensin analogues with different numbers and combinations of disulfide bonds were synthesized and characterized in terms of their NMR solution structures, serum and thermal stabilities, and their antibacterial and membrane-binding activities. Whereas the structures and stabilities of the peptides were primarily dependent on the number and position of the disulfide bonds, their antibacterial and membrane-binding properties were dependent on the cyclic backbone. The results provide insights into the mechanism of action of θ-defensins and illustrate the potential of θ-defensin analogues as scaffolds for peptide drug design.

Item ID: 26691
Item Type: Article (Research - C1)
ISSN: 1083-351X
Keywords: antimicrobial peptides, defensins, disulfide, nuclear magnetic resonance, peptides, cyclic cystine ladder, cyclic peptides, θ-Defensins
Funders: Australian Research Council (ARC)
Projects and Grants: DP0984390
Date Deposited: 03 May 2013 01:01
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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