Cell Selectivity of Arenicin-1 and Its Derivative with Two Disulfide Bonds

摘要

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 a-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-l-C (RWCVYAYCRVRGVLCRYRRCW) by substitution of Val~(8,15) with Cys~(8,15).AR-l-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 a-sheet structures forming a large and flexible ring while AR-l-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 a-sheet structure are important in biological activities of arenicin and its derivative.