title: Discovery of natural products possessing selective eukaryotic readthrough activity: 3-epi-deoxynegamycin and its leucine adduct.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan).
authors.forename: Akihiro
authors.initials: A
authors.lastname: Taguchi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hamada
authors.forename: Masaya
authors.initials: M
authors.lastname: Kotake
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiozuka
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Nakaminami
authors.forename: Thanigaimalai
authors.initials: T
authors.lastname: Pillaiyar
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takayama
authors.forename: Fumika
authors.initials: F
authors.lastname: Yakushiji
authors.forename: Norihisa
authors.initials: N
authors.lastname: Noguchi
authors.forename: Takeo
authors.initials: T
authors.lastname: Usui
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Matsuda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000599:Amino Acids, Diamino / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D018389:Codon, Nonsense; D007930:Leucine / Q000737:chemistry*
chemical_list: D000599:Amino Acids, Diamino; D001688:Biological Products; D018389:Codon, Nonsense; C023434:epi-deoxynegamycin; D007930:Leucine
keywords: (+)-negamycin; natural products; nonsense mutations; peptides; readthrough activity