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Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities

In an effort to develop short antimicrobial peptides with simple amino acid compositions, we generated a series of undecapeptide isomers having the L(5)K(5)W formula. Amino acid sequences were designed to be perfectly amphipathic when folded into a helical conformation by converging leucines onto on...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270530/
https://www.ncbi.nlm.nih.gov/pubmed/23344198
http://dx.doi.org/10.3390/molecules18010859
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author 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
author_facet 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
author_sort Kim, Seo-Jin
collection PubMed
description In an effort to develop short antimicrobial peptides with simple amino acid compositions, we generated a series of undecapeptide isomers having the L(5)K(5)W 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 L(5)K(5)W 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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spelling pubmed-62705302018-12-14 Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities 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 Molecules Article In an effort to develop short antimicrobial peptides with simple amino acid compositions, we generated a series of undecapeptide isomers having the L(5)K(5)W 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 L(5)K(5)W 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. MDPI 2013-01-11 /pmc/articles/PMC6270530/ /pubmed/23344198 http://dx.doi.org/10.3390/molecules18010859 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
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
Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
title Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
title_full Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
title_fullStr Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
title_full_unstemmed Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
title_short Structural Characterization of de Novo Designed L(5)K(5)W Model Peptide Isomers with Potent Antimicrobial and Varied Hemolytic Activities
title_sort structural characterization of de novo designed l(5)k(5)w model peptide isomers with potent antimicrobial and varied hemolytic activities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270530/
https://www.ncbi.nlm.nih.gov/pubmed/23344198
http://dx.doi.org/10.3390/molecules18010859
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