Premium
Discovery of Natural Products Possessing Selective Eukaryotic Readthrough Activity: 3‐ epi ‐Deoxynegamycin and Its Leucine Adduct
Author(s) -
Taguchi Akihiro,
Hamada Keisuke,
Kotake Masaya,
Shiozuka Masataka,
Nakaminami Hidemasa,
Pillaiyar Thanigaimalai,
Takayama Kentaro,
Yakushiji Fumika,
Noguchi Norihisa,
Usui Takeo,
Matsuda Ryoichi,
Hayashi Yoshio
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402208
Subject(s) - antimicrobial , nonsense , nonsense mutation , adduct , biology , drug discovery , leucine , bacteria , chemistry , genetics , biochemistry , gene , amino acid , mutation , microbiology and biotechnology , organic chemistry , missense mutation
Herein we report the first discovery of natural readthrough products that do not display antimicrobial activity. Two natural negamycins, 3‐ epi ‐deoxynegamycin and its leucine adduct, isolated 37 years ago, were found to be potent readthrough agents against nonsense mutations of eukaryotes, but not prokaryotes, without displaying antimicrobial activity. These results suggest that the compounds are valuable leads for the development of readthrough drugs against nonsense‐mediated genetic diseases without the potential for contributing to the emergence of drug‐resistant bacteria.