Structural Characterization of de Novo Designed L5K5W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
AbstractIn an effort to develop short antimicrobial peptides with simple amino acid compositions, we generated a series of undecapeptide isomers having the L5K5W formula. Amino acid sequences were designed to be perfectly amphipathic when folded into a helical conformation by converging leucines onto one side and lysines onto the other side of the helical axis. The single tryptophans, whose positions were varied in the primary structures, were located commonly at the critical amphipathic interface in the helical wheel projection. Helical conformations and the tryptophanyl environments of the 11 L5K5W peptides were confirmed and characterized by circular dichroism, fluorescence and nuclear magnetic resonance spectroscopy. All of the isomers exhibited a potent, broad-spectrum of antibacterial activity with just a slight variance in individual potency, whereas their hemolytic activities against human erythrocytes were significantly diversified. Interestingly, helical dispositions and fluorescence blue shifts of the peptides in aqueous trifluoroethanol solutions, rather than in detergent micelles, showed a marked linear correlation with their hemolytic potency. These results demonstrate that our de novo design strategy for amphipathic helical model peptides is effective for developing novel antimicrobial peptides and their hemolytic activities can be estimated in correlation with structural parameters.
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Kim, S.-J.; Kim, J.-S.; Lee, Y.-S.; Sim, D.-W.; Lee, S.-H.; Bahk, Y.-Y.; Lee, K.-H.; Kim, E.-H.; Park, S.-J.; Lee, B.-J.; Won, H.-S. Structural Characterization of de Novo Designed L5K5W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities. Molecules 2013, 18, 859-876.
Kim S-J, Kim J-S, Lee Y-S, Sim D-W, Lee S-H, Bahk Y-Y, Lee K-H, Kim E-H, Park S-J, Lee B-J, Won H-S. Structural Characterization of de Novo Designed L5K5W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities. Molecules. 2013; 18(1):859-876.Chicago/Turabian Style
Kim, Seo-Jin; Kim, Jae-Seok; Lee, Yoo-Sup; Sim, Dae-Won; Lee, Sung-Hee; Bahk, Young-Yil; Lee, Kwang-Ho; Kim, Eun-Hee; Park, Sung-Jean; Lee, Bong-Jin; Won, Hyung-Sik. 2013. "Structural Characterization of de Novo Designed L5K5W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities." Molecules 18, no. 1: 859-876.