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

Zai, Yu ORCID: https://orcid.org/0000-0002-5813-8753, Ying, Yuan, Ye, Zhuming, Zhou, Mei ORCID: https://orcid.org/0000-0003-2576-0252, Ma, Chengbang, Shi, Zhanzhong, Chen, Xiaoling, Xi, Xinping, Chen, Tianbao ORCID: https://orcid.org/0000-0001-8011-9260 and Wang, Lei ORCID: https://orcid.org/0000-0002-8811-8489 (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) , 627. pp. 1-19. ISSN 2079-6382 [Article] (doi:10.3390/antibiotics9090627)

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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.

Item Type: Article
Additional Information: This article belongs to the Special Issue Synthesis and Utility of Antimicrobial Peptides
Keywords (uncontrolled): antimicrobial peptide, D-amino acid, protease stability, Galleria mellonella larva model
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 31010
Notes on copyright: © 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.
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Depositing User: Jisc Publications Router
Date Deposited: 23 Sep 2020 08:09
Last Modified: 23 Sep 2020 17:49
URI: https://eprints.mdx.ac.uk/id/eprint/31010

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