Nocardiopsins

New FKBP12-binding macrolide polyketides from an Australian marine-derived actinomycete, nocardiopsis sp

Ritesh Raju, Andrew M. Piggott, Melissa Conte, Zakir Tnimov, Kirill Alexandrov, Robert J. Capon

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3194-3200
Number of pages7
JournalChemistry - A European Journal
Volume16
Issue number10
DOIs
Publication statusPublished - 8 Mar 2010
Externally publishedYes

Keywords

  • Immunochemistry macrolides
  • Marine actinomycetes
  • Natural products
  • Polyketides

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