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

• Published in: Bioorganic & medicinal chemistry letters Vol. 3; no. 10; pp. 2039 - 2042
• Main Authors: Balkovec, James M., Black, Regina M., Abruzzo, George K., Bartizal, Ken, Dreikorn, Sarah, Karl, Nollstadt
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.1993
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)81010-6

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.