Cyclopeptide FR235222 isolated from the fermn. broth of Acremonium sp. exhibited a potent inhibition of HDAC (mammalian histone deacetylase), has been synthesized. The first key intermediate for the synthesis of of cyclopeptide, (2S,9R)-2-amino-9-hydroxy-8-oxodecanoic acid (Ahoda), was prepd. from L-Glu via Wittig-Horner-Emmons reaction, and the second key intermediate, trans-4-methyl-D-proline (4-MePro), was prepd. via stereoselective methylation and lactamization.  A 3D model for cyclopeptide inhibitor interaction with the HDAC active site highlights the differences between the binding mode of small-mol. and cyclopeptide inhibitors.

Total Synthesis, NMR Solution Structure, and Binding Model of the Potent Histone Deacetylase Inhibitor FR235222

RODRIQUEZ, Manuela;TERRACCIANO, Stefania;BRUNO, Ines;BIFULCO, Giuseppe;
2006-01-01

Abstract

Cyclopeptide FR235222 isolated from the fermn. broth of Acremonium sp. exhibited a potent inhibition of HDAC (mammalian histone deacetylase), has been synthesized. The first key intermediate for the synthesis of of cyclopeptide, (2S,9R)-2-amino-9-hydroxy-8-oxodecanoic acid (Ahoda), was prepd. from L-Glu via Wittig-Horner-Emmons reaction, and the second key intermediate, trans-4-methyl-D-proline (4-MePro), was prepd. via stereoselective methylation and lactamization.  A 3D model for cyclopeptide inhibitor interaction with the HDAC active site highlights the differences between the binding mode of small-mol. and cyclopeptide inhibitors.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/1518345
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