Structure-Activity Relationship Study of Leucyl-3-epi-deoxynegamycin for Potent Premature Termination Codon Readthrough.

ABSTRACT: (+)-Negamycin, isolated from Streptomyces purpeofuscus, shows antimicrobial activity against Gram-negative bacteria and readthrough activity against nonsense mutations. Previously, we reported that two natural negamycin analogues, 5-deoxy-3-epi-negamycin and its leucine adduct, have more potent readthrough activity in eukaryocytes (COS-7 cells) than negamycin but possess no antimicrobial activity and no in vitro readthrough activity in prokaryotic systems. In the present study, on leucyl-3-epi-deoxynegamycin, a structure-activity relationship study was performed to develop more potent readthrough agents. In a cell-based readthrough assay, the derivative 13b with an o-bromobenzyl ester functions as a prodrug and exhibits a higher readthrough activity against TGA-type PTC than the aminoglyco

SUBMITTER: Taguchi A 

PROVIDER: S-EPMC5642019 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature