Document Detail


Nocardiopsins: new FKBP12-binding macrolide polyketides from an Australian marine-derived actinomycete, Nocardiopsis sp.
MedLine Citation:
PMID:  20112311     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ritesh Raju; Andrew M Piggott; Melissa Conte; Zakir Tnimov; Kirill Alexandrov; Robert J Capon
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemistry (Weinheim an der Bergstrasse, Germany)     Volume:  16     ISSN:  1521-3765     ISO Abbreviation:  Chemistry     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-08     Completed Date:  2010-04-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9513783     Medline TA:  Chemistry     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3194-200     Citation Subset:  IM    
Affiliation:
Institute for Molecular Bioscience, The University of Queensland, Carmody Road, St. Lucia, Brisbane 4072, Australia.
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MeSH Terms
Descriptor/Qualifier:
Actinobacteria / chemistry*,  isolation & purification*
Animals
Anti-Bacterial Agents / chemistry*,  isolation & purification*
Immunochemistry / methods
Immunosuppressive Agents / chemistry*
Macrolides / chemistry*,  isolation & purification*,  metabolism
Marine Biology
Molecular Structure
Sirolimus / chemistry*
Tacrolimus / chemistry*
Tacrolimus Binding Protein 1A / chemistry*,  isolation & purification*,  metabolism
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Immunosuppressive Agents; 0/Macrolides; 0/nocardiopsin A; 0/nocardiopsin B; 109581-93-3/Tacrolimus; 53123-88-9/Sirolimus; EC 5.2.1.-/Tacrolimus Binding Protein 1A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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