(1) Merck and Company, P.O. Box 2000, 07065 Rahway, Building 80Y-310, NJ, USA;(2) Merck Sharp & Dohme de España, S. A. Josefa Valcarcel 38, 28027 Madrid, Spain;(3) Merck Research Laboratories, Sumneytown Pike, 19486 West Point, PA, USA
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.