FKBP12: FK506 (macrolide isolated from Streptomyces tsukubaensis)-Binding Protein 12
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Full Paper
Nocardiopsins: New FKBP12-Binding Macrolide Polyketides from an Australian Marine-Derived Actinomycete, Nocardiopsis sp.†
Article first published online: 28 JAN 2010
DOI: 10.1002/chem.200902933
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Raju, R., Piggott, Andrew M., Conte, M., Tnimov, Z., Alexandrov, K. and Capon, Robert J. (2010), Nocardiopsins: New FKBP12-Binding Macrolide Polyketides from an Australian Marine-Derived Actinomycete, Nocardiopsis sp.Chem. Eur. J., 16: 3194–3200. doi: 10.1002/chem.200902933
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Publication History
- Issue published online: 1 MAR 2010
- Article first published online: 28 JAN 2010
- Manuscript Received: 23 OCT 2009
Funded by
- Institute for Molecular Bioscience
- University of Queensland
Keywords:
- immunochemistry;
- macrolides;
- marine actinomycetes;
- natural products;
- polyketides
Abstract
A marine-derived actinomycete, Nocardiopsis sp. (CMB-M0232), obtained from a sediment sample collected at a depth of 55 m off the coast of Brisbane, Australia, yielded two new macrolide polyketides. Structures for nocardiopsins A and B were assigned by detailed spectroscopic analysis, degradation and chemical derivatization. A Marfey’s analysis revealed an unexpected acid-mediated partial racemization of the L-pipecolic acid incorporated within the nocardiopsins. The scope of this racemization was assessed against a selection of natural and synthetic N-acyl pipecolic acids. While the nocardiopsins are not antibacterial, antifungal or cytotoxic, they do exhibit low-micromolar binding to the immunophilin FKBP12, consistent with their structural and biosynthetic relationship to the immunosuppressive agents FK506 and rapamycin. The nocardiopsins represent a new point of entry into what has been a valuable, exclusive and reclusive region of bioactive chemical space—that surrounding the FK506/rapamycin pharmacophore.