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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

Activity Optimization of an Undecapeptide Analogue Derived from a Frog-Skin Antimicrobial Peptide

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

Received: August 10, 2010; Revised: September 26, 2010; Accepted: October 14, 2010

Abstract

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

Article

Research Article

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.

Activity Optimization of an Undecapeptide Analogue Derived from a Frog-Skin Antimicrobial Peptide

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

Received: August 10, 2010; Revised: September 26, 2010; Accepted: October 14, 2010

Abstract

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
Feb 28, 2023 Vol.46 No.2, pp. 69~129
COVER PICTURE
The bulk tissue is a heterogeneous mixture of various cell types, which is depicted as a skein of intertwined threads with diverse colors each of which represents a unique cell type. Single-cell omics analysis untangles efficiently the skein according to the color by providing information of molecules at individual cells and interpretation of such information based on different cell types. The molecules that can be profiled at the individual cell by single-cell omics analysis includes DNA (bottom middle), RNA (bottom right), and protein (bottom left). This special issue reviews single-cell technologies and computational methods that have been developed for the single-cell omics analysis and how they have been applied to improve our understanding of the underlying mechanisms of biological and pathological phenomena at the single-cell level.

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