title: The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product.
abstract: Reaction of cellular thiols with the 1,2-dithiolan-3-one 1-oxide moiety of leinamycin triggers the generation of DNA-damaging reactive intermediates. Studies with small, synthetic analogues of leinamycin reveal that the macrocyclic portion of the natural product imparts remarkable hydrolytic stability to the 1,2-dithiolan-3-one 1-oxide heterocycle without substantially compromising its thiol-sensing property.
authors.affiliation: Department of Chemistry, University of Missouri, Columbia, MO 65211, United States.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Sivaramakrishnan
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.forename: Daekyu
authors.initials: D
authors.lastname: Sun
authors.forename: Kent S
authors.initials: KS
authors.lastname: Gates
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage; D004249:DNA Damage; D006868:Hydrolysis; D007769:Lactams / Q000737:chemistry*; D018942:Macrolides / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*; D013871:Thiones / Q000737:chemistry*
chemical_list: D001688:Biological Products; D007769:Lactams; D018942:Macrolides; D010087:Oxides; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin; D004247:DNA