title: Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase.
abstract: Actinoplanic acids A and B are macrocyclic polycarboxylic acids that are potent reversible inhibitors of farnesyl-protein transferase. Actinoplanic acids A and B were isolated from Actinoplanes sp. MA 7066 while actinoplanic acid B was isolated from both MA 7066 and Streptomyces sp. MA 7099. Actinoplanic acids A and B are competitive with respect to farnesyl diphosphate and are selective inhibitors of farnesyl-protein transferase because they do not inhibit geranylgeranyl-protein transferase type 1 or squalene synthase. MA 7066 is believed to be a novel species of actinomycetes while MA 7099 is believed to be a novel strain of Streptomyces violaceusniger on the basis of morphological, biochemical and chemotaxonomic characteristics as well as its production of actinoplanic acids.
authors.affiliation: Merck and Company, Rahway, NJ 07065, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Silverman
authors.forename: C
authors.initials: C
authors.lastname: Cascales
authors.forename: O
authors.initials: O
authors.lastname: Genilloud
authors.forename: J M
authors.initials: JM
authors.lastname: Sigmund
authors.forename: S E
authors.initials: SE
authors.lastname: Gartner
authors.forename: G E
authors.initials: GE
authors.lastname: Koch
authors.forename: M M
authors.initials: MM
authors.lastname: Gagliardi
authors.forename: B K
authors.initials: BK
authors.lastname: Heimbuch
authors.forename: M
authors.initials: M
authors.lastname: Nallin-Omstead
authors.forename: M
authors.initials: M
authors.lastname: Sanchez
mesh_terms: D000192:Actinomycetales / Q000737:chemistry*; D019883:Alkyl and Aryl Transferases; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D007783:Lactones / Q000302:isolation & purification* / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry*; D014166:Transferases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007783:Lactones; C096084:actinoplanic acid A; C096085:actinoplanic acid B; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase