Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase.
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.
Silverman
K C
KC
Merck and Company, Rahway, NJ 07065, USA.
Cascales
C
C
Genilloud
O
O
Sigmund
J M
JM
Gartner
S E
SE
Koch
G E
GE
Gagliardi
M M
MM
Heimbuch
B K
BK
Nallin-Omstead
M
M
Sanchez
M
M
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*
D004791:Enzyme Inhibitors; D007783:Lactones; C096084:actinoplanic acid A; C096085:actinoplanic acid B; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase