Arginine-linked neomycin B dimers: synthesis, rRNA binding, and resistance enzyme activity.

ABSTRACT: The nucleotides comprising the ribosomal decoding center are highly conserved, as they are important for maintaining translational fidelity. The bacterial A-site has a small base variation as compared with the human analogue, allowing aminoglycoside (AG) antibiotics to selectively bind within this region of the ribosome and negatively affect microbial protein synthesis. Here, by using a fluorescence displacement screening assay, we demonstrate that neomycin B (NEO) dimers connected by L-arginine-containing linkers of varying length and composition bind with higher affinity to model A-site RNAs compared to NEO, with IC₅₀ values ranging from ~40-70 nM, and that a certain range of linker lengths demonstrates a clear preference for the bacterial A-site RNA over the human analogue. F

SUBMITTER: Jin Y 

PROVIDER: S-EPMC4722958 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature