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Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase

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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.

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Authors and Affiliations

  1. Merck and Company, P.O. Box 2000, 07065, Rahway, Building 80Y-310, NJ, USA

    K. C. Silverman, J. M. Sigmund, S. E. Gartner, G. E. Koch, M. M. Gagliardi, B. K. Heimbuch, M. Nallin-Omstead, G. M. Garrity, C. F. Hirsch, S. B. Singh & R. B. Lingham

  2. Merck Sharp & Dohme de España, S. A. Josefa Valcarcel 38, 28027, Madrid, Spain

    C. Cascales, O. Genilloud, M. Sanchez, M. T. Diez & I. Martin

  3. Merck Research Laboratories, Sumneytown Pike, 19486, West Point, PA, USA

    J. B. Gibbs

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  1. K. C. Silverman
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  2. C. Cascales
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  3. O. Genilloud
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  4. J. M. Sigmund
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  5. S. E. Gartner
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  6. G. E. Koch
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  7. M. M. Gagliardi
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  9. M. Nallin-Omstead
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  10. M. Sanchez
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  11. M. T. Diez
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  12. I. Martin
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  14. C. F. Hirsch
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  15. J. B. Gibbs
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Silverman, K.C., Cascales, C., Genilloud, O. et al. Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase. Appl Microbiol Biotechnol 43, 610–616 (1995). https://doi.org/10.1007/BF00164762

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  • DOI: https://doi.org/10.1007/BF00164762

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