Design and Synthesis of Paromomycin-Related Heterocycle-Substituted Aminoglycoside Mimetics Based on a Mass Spectrometry RNA-Binding Assay

摘要

The family of aminoglycosides, which includes neomycin, paromomycin (1), lividomycin, kanamycin, and gentamicin, is the RNA of the small ribosomal subunit. This bactericidal action is mediated by binding of the compound to the bacterial RNA in a way that leads to misreading of the genetic code. The decoding region of the 16S ribosomal RNA contains a smaller subdomain (16S) that folds and retains the key structural features of the full-length RNA. This "A-site" subdomain binds aminoglycosides at the same location as the intact rRNA.