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
TypeArticle
TitleBroad-spectrum antimicrobial activity and improved stability of a D-Amino acid enantiomer of DMPC-10A, the designed derivative of dermaseptin truncates
AuthorsZai, 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.

Keywordsantimicrobial peptide, D-amino acid, protease stability, Galleria mellonella larva model
PublisherMDPI AG
JournalAntibiotics
ISSN2079-6382
Publication dates
Online21 Sep 2020
Print21 Sep 2020
Publication process dates
Deposited23 Sep 2020
Submitted26 Aug 2020
Accepted17 Sep 2020
Output statusPublished
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Copyright Statement

© 2020 by the authors.
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

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
LanguageEnglish
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