The purpose of this study is to understand the interactions of some antibacterial cationic amphipathic cyclooctapeptides with calcium(II) and their secondary structural preferences. The thermodynamic parameters associated with calcium(II) interactions, between the antibacterial active cyclooctapeptides (COP 1–6) and those that did not exhibit significant activities (COP 7–9), were studied by isothermal titration calorimetry. Calcium(II) binding in the absence and presence of micellar dodecylphosphocholine (DPC), a membrane mimicking detergent, was conducted by circular dichroism (CD). Both groups of cyclopeptides showed weak binding affinities for calcium(II) (Kb ca. 10？3？M？1). However, CD data showed that the antimicrobial peptides COP 1–6 adopted a twisted beta-sheet structure (positive CD absorption band at ca. 203？nm) in the presence of calcium(II) in micellar DPC. In contrast, COP 7–9, which lacked antibacterial activity, adopted a different conformational structure (negative CD absorption band at ca. 203？nm). These results indicate that these cyclopeptides could adopt secondary structural preferences in the presence of calcium(II) amidst a hydrophobic environment to elicit their antibacterial activity. These findings could be useful in facilitating the design of cyclopeptide derivatives that can adopt this beta-sheet-like secondary structure and, thereby, provide a useful molecular template for crafting antibacterial compounds. 1. Introduction Antimicrobial peptides (AMP) are a promising type of antibacterials [1, 2]. These compounds usually share a common site of action: the bacterial membrane. They usually exhibit strong selectivity toward the target bacterial membranes and kill rapidly. Amongst this class of compounds are the polycationic alpha helical peptides such as gramicidin A [3], melittin [4], cecropin [5], and magainin [6, 7], which play a significant role in host defense against bacteria. Other attractive antimicrobial candidates from this class are the macrocyclic peptides, which also target bacterial membranes and could elude bacterial resistance. Interest in cyclic peptides began following the discovery of gramicidin S, a cyclic decapeptide antibiotic produced by a strain of Bacillus brevis [8]. Hodges et al. synthesized analogues of gramicidin S and examined the role of hydrophobicity in microbial specificity. Although they found that the therapeutic window could be optimized for each type of bacteria by modulation of peptide hydrophobicity, their results showed that the structure and antimicrobial activity relationship is
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