title: Degradation and reconstruction of moenomycin A and derivatives: dissecting the function of the isoprenoid chain.
abstract: Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by binding the bacterial transglycosylases. We describe a degradation/reconstruction route to manipulate the reducing end of moenomycin A. A comparison of the biological and enzyme inhibitory activity of moenomycin A and an analogue containing a nerol lipid in place of the natural C25 lipid chain provides insight into the role of the moenocinol unit. Our results show that a lipid chain having ten carbons in moenocinol is sufficient for enzyme inhibition, but a longer chain is required for biological acitivity, apparently because the molecule must partition into biological membranes to reach its target in bacterial cells.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Masaatsu
authors.initials: M
authors.lastname: Adachi
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Catherine
authors.initials: C
authors.lastname: Leimkuhler
authors.forename: Binyuan
authors.initials: B
authors.lastname: Sun
authors.forename: John V
authors.initials: JV
authors.lastname: LaTour
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kahne
mesh_terms: D001455:Bambermycins / Q000737:chemistry*; D002240:Carbohydrate Sequence; D006868:Hydrolysis; D008969:Molecular Sequence Data; D013729:Terpenes / Q000737:chemistry*
chemical_list: D013729:Terpenes; D001455:Bambermycins; C437243:moenomycin A