Secondary Structural Preferences of Some Antibacterial Cyclooctapeptides in the Presence of Calcium(II)

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.