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  • Title: New fungal metabolite geranylgeranyltransferase inhibitors with antifungal activity.
    Author: Singh SB, Kelly R, Guan Z, Polishook JD, Domrowski AW, Collado J, Gonzalez A, Pelaez F, Register E, Kelly TM, Bonfiglio C, Williamson JM.
    Journal: Nat Prod Res; 2005 Dec; 19(8):739-47. PubMed ID: 16317828.
    Abstract:
    Geranylgeranyltransferase I (GGTase I) catalyzes the post-translational transfer of lyophilic diterpenoid geranylgeranyl to the cysteine residue of proteins terminating with a CaaX motif such as Rho1p and Cdc42p. It has been shown that GGTase I activity is essential for viability of Saccharomyces cerevisiae and hence its inhibition is a potential antifungal target. From natural product screening, a number of azaphilones including one novel analog were isolated as broad-spectrum inhibitors of GGTase I. Isolation, structure elucidation, GGTase I inhibitory activities and antifungal activities of these compounds are described.
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