Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates

Yu Zai; Yuan Ying; Zhuming Ye; Mei Zhou; Chengbang Ma; Zhanzhong Shi; Xiaoling Chen; Xinping Xi; Tianbao Chen; Lei Wang

doi:10.3390/antibiotics9090627

Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates

Yu Zai, Yuan Ying, Zhuming Ye, Mei Zhou, Chengbang Ma, Zhanzhong Shi, Xiaoling Chen, Xinping Xi, Tianbao Chen, Lei Wang

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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Abstract

DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.

Original language	English
Article number	627
Pages (from-to)	1-19
Number of pages	19
Journal	Antibiotics
Volume	9
Issue number	9
DOIs	https://doi.org/10.3390/antibiotics9090627
Publication status	Published - 21 Sept 2020

Keywords

antimicrobial peptide; D-amino acid; protease stability; Galleria mellonella larva model

ASJC Scopus subject areas

Microbiology
Biochemistry
Pharmacology, Toxicology and Pharmaceutics(all)
Microbiology (medical)
Infectious Diseases
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/antibiotics9090627Licence: CC BY

Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates
Copyright 2020 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.93 MBLicence: CC BY

Identification, characterisation and design of bioactive peptides from Chinese frogs
Zai, Y. (Author), Zhou, M. (Supervisor), Wang, L. (Supervisor), Xi, X. (Supervisor) & Chen, T. (Supervisor), Dec 2020
Student thesis: Doctoral Thesis › Doctor of Philosophy
Identification, characterization and bioevaluation of a bioactive peptide from the skin secretion of the Chinese forest frog
Ye, Z. (Author), Zhou, M. (Supervisor), Wang, L. (Supervisor), Chen, T. (Supervisor) & Xi, X. (Supervisor), Dec 2021
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

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title = "Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates",

abstract = "DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.",

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author = "Yu Zai and Yuan Ying and Zhuming Ye and Mei Zhou and Chengbang Ma and Zhanzhong Shi and Xiaoling Chen and Xinping Xi and Tianbao Chen and Lei Wang",

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AU - Zai, Yu

AU - Ying, Yuan

AU - Ye, Zhuming

AU - Zhou, Mei

AU - Ma, Chengbang

AU - Shi, Zhanzhong

AU - Chen, Xiaoling

AU - Xi, Xinping

AU - Chen, Tianbao

AU - Wang, Lei

PY - 2020/9/21

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N2 - DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.

AB - DMPC-10A (ALWKKLLKK-Cha-NH2) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala1 and Trp3 remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae using the Galleria mellonella larva model and displayed synergistic activities with gentamicin against carbapenem-resistant K. pneumoniae strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.

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Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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Student theses

Identification, characterisation and design of bioactive peptides from Chinese frogs

Identification, characterization and bioevaluation of a bioactive peptide from the skin secretion of the Chinese forest frog

Cite this