Solution structures and biological functions of the antimicrobial peptide, arenicin-1, and its linear derivative

Arenicin‐1 (AR‐1) is a novel antimicrobial peptide that was isolated from coelomocytes of the marine polychaeta lugworm Arenicola marina and shown to contain a single disulfide bond between Cys3 and Cys20, forming an 18‐residue ring [Ovchinnikova, T. V. et al., FEBS Lett 2004, 577, 209–214]. To determine the role of this disulfide bond, we synthesized AR‐1 (RWCVYAYVRVRGVLVRYRRCW) and its linear derivative, arenicin‐1‐S (AR‐1‐S: RWSVYAYVRVRGVLVRYRRSW). Activity assays revealed that AR‐1‐S is somewhat less active against bacterial cells than AR‐1. Both peptides were very hydrophobic, and displayed cytotoxicity against human red blood cells. Analysis of the tertiary structures of AR‐1 and AR‐1‐S by NMR spectroscopy disclosed that AR‐1 has two‐stranded antiparallel β‐sheet structures with amphipathicity, while AR‐1‐S displays a random coil structure in DMSO. Our biological data for AR‐1 and AR‐1‐S indicate that the hydrophobic‐hydrophilic balance, disulfide bridge, and the amphipathic β‐sheet structure of the peptides play important roles in their biological activities. Elucidation of the structure of AR‐1 and its derivative should facilitate the design of novel non‐cytotoxic peptide antibiotics with potent antibacterial activities. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 208–216, 2007. This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com