Antimicrobial Peptides Incorporating Halogenated Marine-Derived Amino Acid Substituents.


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
08 Jun 2023
Historique:
received: 15 03 2023
accepted: 01 05 2023
pmc-release: 08 06 2024
medline: 14 6 2023
pubmed: 14 6 2023
entrez: 14 6 2023
Statut: epublish

Résumé

Small synthetic mimics of cationic antimicrobial peptides represent a promising class of compounds with leads in clinical development for the treatment of persistent microbial infections. The activity and selectivity of these compounds rely on a balance between hydrophobic and cationic components, and here, we explore the activity of 19 linear cationic tripeptides against five different pathogenic bacteria and fungi, including clinical isolates. The compounds incorporated modified hydrophobic amino acids inspired by motifs often found in bioactive marine secondary metabolites in combination with different cationic residues to probe the possibility of generating active compounds with improved safety profiles. Several of the compounds displayed high activity (low μM concentrations), comparable with the positive controls AMC-109, amoxicillin, and amphotericin B. A higher activity was observed against the fungal strains, and a low

Identifiants

pubmed: 37312845
doi: 10.1021/acsmedchemlett.3c00093
pmc: PMC10258904
doi:

Types de publication

Journal Article

Langues

eng

Pagination

802-809

Informations de copyright

© 2023 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Alexander J Craig (AJ)

Drug Design and Discovery, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.
Analytical Chemistry, Department of Chemistry, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.

Yuri Ermolovich (Y)

Department of Drug Design and Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark.

Alan Cameron (A)

School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand.

Agnes Rodler (A)

Department of Pharmacy, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.

Helen Wang (H)

Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.

Jeffrey A Hawkes (JA)

Analytical Chemistry, Department of Chemistry, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.

Madlen Hubert (M)

Department of Pharmacy, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.

Fredrik Björkling (F)

Department of Drug Design and Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark.

Natalia Molchanova (N)

The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Margaret A Brimble (MA)

School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand.

Lindon W K Moodie (LWK)

Drug Design and Discovery, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.
Uppsala Antibiotic Centre, Biomedical Centre, Uppsala University, 75123 Uppsala, Sweden.

Johan Svenson (J)

Cawthron Institute, 98 Halifax Street East, Nelson 7010, New Zealand.

Classifications MeSH