TY - JOUR
T1 - Nocardiopsins
T2 - New FKBP12-binding macrolide polyketides from an Australian marine-derived actinomycete, nocardiopsis sp
AU - Raju, Ritesh
AU - Piggott, Andrew M.
AU - Conte, Melissa
AU - Tnimov, Zakir
AU - Alexandrov, Kirill
AU - Capon, Robert J.
PY - 2010/3/8
Y1 - 2010/3/8
N2 - 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.
AB - 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.
KW - Immunochemistry macrolides
KW - Marine actinomycetes
KW - Natural products
KW - Polyketides
UR - http://www.scopus.com/inward/record.url?scp=77649210115&partnerID=8YFLogxK
U2 - 10.1002/chem.200902933
DO - 10.1002/chem.200902933
M3 - Article
C2 - 20112311
AN - SCOPUS:77649210115
VL - 16
SP - 3194
EP - 3200
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 10
ER -