Structure-Based Design and Synthesis of Apramycin-Paromomycin Analogues: Importance of the Configuration at the 6'-Position and Differences between the 6'-Amino and Hydroxy Series.

ABSTRACT: The preparation of a series of four analogues of the aminoglycoside antibiotics neomycin and paromomycin is described in which ring I, involved in critical binding interactions with the ribosomal target, is replaced by an apramycin-like dioxabicyclo[4.4.0]octane system. The effect of this modification is to lock the hydroxymethyl side chain of the neomycin or paromomycin ring I, as part of the dioxabicyclooctane ring, into either the gauche-gauche or the gauche-trans conformation (respectively, axial or equatorial to the bicyclic system). The antiribosomal activity of these compounds is investigated with cell-free translation assays using both bacterial ribosomes and recombinant hybrid ribosomes carrying eukaryotic decoding A site cassettes. Compounds substituted with an equatorial hydroxy

SUBMITTER: Mandhapati AR 

PROVIDER: S-EPMC5647259 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature