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Merging Natural Products: Muraymycin-Sansanmycin Hybrid Structures as Novel Scaffolds for Potential Antibacterial Agents.


ABSTRACT: To overcome bacterial resistances, the need for novel antimicrobial agents is urgent. The class of so-called nucleoside antibiotics furnishes promising candidates for the development of new antibiotics, as these compounds block a clinically unexploited bacterial target: the integral membrane protein MraY, a key enzyme in cell wall (peptidoglycan) biosynthesis. Nucleoside antibiotics exhibit remarkable structural diversity besides their uridine-derived core motifs. Some sub-classes also show specific selectivities towards different Gram-positive and Gram-negative bacteria, which are poorly understood so far. Herein, the synthesis of a novel hybrid structure is reported, derived from the 5'-defunctionalized uridine core moiety of muraymycins and the peptide chain of sansanmycin B, as a new scaffold for the development of antimicrobial agents. The reported muraymycin-sansanmycin hybrid scaffold showed nanomolar activity against the bacterial target enzyme MraY, but displayed no significant antibacterial activity against S.?aureus, E.?coli, and P.?aeruginosa.

SUBMITTER: Niro G 

PROVIDER: S-EPMC7756498 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Merging Natural Products: Muraymycin-Sansanmycin Hybrid Structures as Novel Scaffolds for Potential Antibacterial Agents.

Niro Giuliana G   Weck Stefanie C SC   Ducho Christian C  

Chemistry (Weinheim an der Bergstrasse, Germany) 20201116 70


To overcome bacterial resistances, the need for novel antimicrobial agents is urgent. The class of so-called nucleoside antibiotics furnishes promising candidates for the development of new antibiotics, as these compounds block a clinically unexploited bacterial target: the integral membrane protein MraY, a key enzyme in cell wall (peptidoglycan) biosynthesis. Nucleoside antibiotics exhibit remarkable structural diversity besides their uridine-derived core motifs. Some sub-classes also show spec  ...[more]

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