Broad-spectrum antimicrobial activity and improved stability of a D-Amino acid enantiomer of DMPC-10A, the designed derivative of dermaseptin truncates
Article
Zai, Y., Ying, Y., Ye, Z., Zhou, M., Ma, C., Shi, Z., Chen, X., Xi, X., Chen, T. and Wang, L. 2020. Broad-spectrum antimicrobial activity and improved stability of a D-Amino acid enantiomer of DMPC-10A, the designed derivative of dermaseptin truncates. Antibiotics. 9 (9), pp. 1-19. https://doi.org/10.3390/antibiotics9090627
Type | Article |
---|---|
Title | Broad-spectrum antimicrobial activity and improved stability of a D-Amino acid enantiomer of DMPC-10A, the designed derivative of dermaseptin truncates |
Authors | Zai, Y., Ying, Y., Ye, Z., Zhou, M., Ma, C., Shi, Z., Chen, X., Xi, X., Chen, T. and Wang, L. |
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. |
Keywords | antimicrobial peptide, D-amino acid, protease stability, Galleria mellonella larva model |
Publisher | MDPI AG |
Journal | Antibiotics |
ISSN | 2079-6382 |
Publication dates | |
Online | 21 Sep 2020 |
21 Sep 2020 | |
Publication process dates | |
Deposited | 23 Sep 2020 |
Submitted | 26 Aug 2020 |
Accepted | 17 Sep 2020 |
Output status | Published |
Publisher's version | License |
Copyright Statement | © 2020 by the authors. |
Additional information | This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides |
Digital Object Identifier (DOI) | https://doi.org/10.3390/antibiotics9090627 |
Language | English |
https://repository.mdx.ac.uk/item/89146
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