Pneumocandin antifungal lipopeptides. The phenolic hydroxyl is required for 1,3-β-glucan synthesis inhibition

Pneumocandin B 0 1 undergoes selective oxidation / reduction chemistry at the homotyrosine ( hty) residue. Removal of the phenolic hydroxyl gives >140-fold loss in activity against a Candida albicans 1,3-β-glucan synthetase enzyme preparation and a significant loss of antifungal activity. Inversi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1993-10, Vol.3 (10), p.2039-2042
Main Authors: Balkovec, James M., Black, Regina M., Abruzzo, George K., Bartizal, Ken, Dreikorn, Sarah, Karl, Nollstadt
Format: Article
Language:English
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Summary:Pneumocandin B 0 1 undergoes selective oxidation / reduction chemistry at the homotyrosine ( hty) residue. Removal of the phenolic hydroxyl gives >140-fold loss in activity against a Candida albicans 1,3-β-glucan synthetase enzyme preparation and a significant loss of antifungal activity. Inversion of the C4- hty hydroxyl causes about a 70-fold decrease in potency, while removal of this hydroxyl yields a more potent inhibitor. Pneumocandin B 0 1 undergoes selective oxidation / reduction chemistry at the homotyrosine ( hty) residue. Removal of the phenolic hydroxyl gives >140-fold loss in activity against a Candida albicans 1,3-β-glucan synthetase enzyme and a significant loss of antifungal activity. Inversion of the C4- hty hydroxyl causes about a 70-fold decrease in activity, while removal of this hydroxyl gives a more potent inhibitor.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(01)81010-6