Mol. Cells 2011; 31(1): 49-54
Published online November 23, 2010
https://doi.org/10.1007/s10059-011-0005-y
© The Korean Society for Molecular and Cellular Biology
Correspondence to : *Correspondence: lbj@nmr.snu.ac.kr
While natural antimicrobial peptides are potential thera-peutic agents, their physicochemical properties and bioactivity generally need to be enhanced for clinical and commercial development. We have previously developed a cationic, amphipathic α-helical, 11-residue peptide (named herein GA-W2: FLGWLFKWASK-NH2) with potent antimicrobial and hemolytic activity, which was derived from a 24-residue, natural antimicrobial peptide isolated from frog skin. Here, we attempted to optimize peptide bioactivity by a rational approach to sequence modification. Seven analogues were generated from GA-W2, and their activities were compared with that of a 12-residue peptide, omiganan, which is being developed for clinical and commercial applications. Most of the modifications reported here improved antimicrobial activity. Among them, the GA-K4AL (FAKWAFKWLKK-NH2) peptide displayed the most potent antimicrobial activity with negligible hemolytic activity, superior to that of omiganan. The therapeutic index of GA-K4AL was improved more than 53- and more than 31-fold against Gram-negative and Gram-positive bacteria, respectively, compared to that of the starting peptide, GA-W2. Given its relatively shorter length and simpler amino acid composition, our sequence-optimized GA-K4AL peptide may thus be a potentially useful antimicrobial peptide agent.
Keywords activity optimization, amphipathic helix, antimicrobial activity, antimicrobial peptide, hemolytic activity, sequence modification
Mol. Cells 2011; 31(1): 49-54
Published online January 31, 2011 https://doi.org/10.1007/s10059-011-0005-y
Copyright © The Korean Society for Molecular and Cellular Biology.
Hyung-Sik Won1,2,6, Su-Jin Kang3,6, Wahn-Soo Choi4, and Bong-Jin Lee1,3,5,*
1Structural Research Center for Innovative Drug Discovery, Seoul National University, Seoul 151-742, Korea, 2Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea, 3Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea, 4Department of Immunology, College of Medicine, Konkuk University, Chungju 380-701, Korea, 5Promeditech Inc., Seoul 151-011, Korea, 6These authors contributed equally to this work.
Correspondence to:*Correspondence: lbj@nmr.snu.ac.kr
While natural antimicrobial peptides are potential thera-peutic agents, their physicochemical properties and bioactivity generally need to be enhanced for clinical and commercial development. We have previously developed a cationic, amphipathic α-helical, 11-residue peptide (named herein GA-W2: FLGWLFKWASK-NH2) with potent antimicrobial and hemolytic activity, which was derived from a 24-residue, natural antimicrobial peptide isolated from frog skin. Here, we attempted to optimize peptide bioactivity by a rational approach to sequence modification. Seven analogues were generated from GA-W2, and their activities were compared with that of a 12-residue peptide, omiganan, which is being developed for clinical and commercial applications. Most of the modifications reported here improved antimicrobial activity. Among them, the GA-K4AL (FAKWAFKWLKK-NH2) peptide displayed the most potent antimicrobial activity with negligible hemolytic activity, superior to that of omiganan. The therapeutic index of GA-K4AL was improved more than 53- and more than 31-fold against Gram-negative and Gram-positive bacteria, respectively, compared to that of the starting peptide, GA-W2. Given its relatively shorter length and simpler amino acid composition, our sequence-optimized GA-K4AL peptide may thus be a potentially useful antimicrobial peptide agent.
Keywords: activity optimization, amphipathic helix, antimicrobial activity, antimicrobial peptide, hemolytic activity, sequence modification
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