Cell selectivity of arenicin-1 and its derivative with two disulfide bonds

Abstract

Antibiotics has become more important in modern health care system. Antimicrobial peptide is one of the attractive candidates for new mechanism of antibiotics. Arenicin-1 (AR-1) is 21-residue antimicrobial peptide isolated from marine polychaeta Arenicola marina with single disulfide bond forming an 18-residue ring [Ovchinnikova, T. V. et al., FEBS Lett. 2004, 577, 209-214]. Our previous study on AR-1 and its linear derivative showed that disulfide bridge and the amphipathic â-sheet structure of the AR-1 play important roles in their biological activities. AR-1 has high antibacterial activity but it also displays hemolytic activity against human red blood cells. In order to develop more potent and more bacterial cell selective peptide, we designed and synthesized a new derivative, AR-1-C (RWCVYAYCRVRGVLCRYRRCW) by substitution of Val8,15 with Cys8,15. AR-1-C has higher antibacterial activity but displayed less hemolytic activity against human red blood cells than the parent AR-1. AR-1 has a two-stranded antiparallel â-sheet structures forming a large and flexible ring while AR-1-C with two disulfide bonds forming a 12-residue ring has higher structural rigidity and higher hydrophobic-hydrophilic balance than AR-1. Peptide rigidity and optimum balance between the hydrophobic and hydrophilic phase in amphipathic â-sheet structure are important in biological activities of arenicin and its derivative.