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

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

The Journal of biological chemistry (2013-02-23)
Anne C Conibear, K Johan Rosengren, Norelle L Daly, Sónia Troeira Henriques, David J Craik
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Supelco
L-Cystine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
L-Cystine, produced by Wacker Chemie AG, Burghausen, Germany, ≥98.5%
SAFC
L-Cystine
Sigma-Aldrich
L-Cystine, from non-animal source, meets EP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Cystine, ≥98% (TLC), crystalline
Sigma-Aldrich
L-Cystine, ≥99.7% (TLC)
Cystine, European Pharmacopoeia (EP) Reference Standard