Dataset Information

Conjugates of Aminoglycosides with Stapled Peptides as a Way to Target Antibiotic-Resistant Bacteria.

ABSTRACT: The misuse and overuse of antibiotics led to the development of bacterial resistance to existing aminoglycoside (AMG) antibiotics and limited their use. Consequently, there is a growing need to develop effective antimicrobials against multidrug-resistant bacteria. To target resistant strains, we propose to combine 2-deoxystreptamine AMGs, neomycin (NEO) and amikacin (AMK), with a membrane-active antimicrobial peptide anoplin and its hydrocarbon stapled derivative. The AMG-peptide hybrids were conjugated using the click chemistry reaction in solution to obtain a non-cleavable triazole linker and by disulfide bridge formation on the resin to obtain a linker cleavable in the bacterial cytoplasm. Homo-dimers connected via disulfide bridges between the N-terminus thiol analogues of anoplin and hydrocarbon stapled anoplin were also synthesized. These hybrid compounds show a notable increase in antibacterial and bactericidal activity, as compared to the unconjugated ones or their combinations, against Gram-positive and Gram-negative bacteria, especially for the strains resistant to AMK or NEO. The conjugates and disulfide peptide dimers exhibit low hemolytic activity on sheep red blood erythrocytes.

SUBMITTER: Macyszyn J

PROVIDER: S-EPMC10233823 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Conjugates of Aminoglycosides with Stapled Peptides as a Way to Target Antibiotic-Resistant Bacteria.

Macyszyn Julia J Burmistrz Michał M Mieczkowski Adam A Wojciechowska Monika M Trylska Joanna J

ACS omega 20230516 21

The misuse and overuse of antibiotics led to the development of bacterial resistance to existing aminoglycoside (AMG) antibiotics and limited their use. Consequently, there is a growing need to develop effective antimicrobials against multidrug-resistant bacteria. To target resistant strains, we propose to combine 2-deoxystreptamine AMGs, neomycin (NEO) and amikacin (AMK), with a membrane-active antimicrobial peptide anoplin and its hydrocarbon stapled derivative. The AMG-peptide hybrids were co ...[more]

PMID: 37273645

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Dataset Information

Conjugates of Aminoglycosides with Stapled Peptides as a Way to Target Antibiotic-Resistant Bacteria.

Publications

Conjugates of Aminoglycosides with Stapled Peptides as a Way to Target Antibiotic-Resistant Bacteria.

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