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Total Synthesis, NMR Solution Structure, and Binding Model of the Potent Histone Deacetylase Inhibitor FR235222
Author(s) -
Rodriquez Manuela,
Terracciano Stefania,
Cini Elena,
Settembrini Giulia,
Bruno Ines,
Bifulco Giuseppe,
Taddei Maurizio,
GomezPaloma Luigi
Publication year - 2006
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200501995
Subject(s) - histone deacetylase inhibitor , histone deacetylase , chemistry , metabolite , stereochemistry , biochemistry , small molecule , amino acid , histone , computational biology , biology , gene
An alternative route : The fungal metabolite FR235222, a potent inhibitor of mammalian histone deacetylase (HDAC), has been synthesized. Key steps are the preparation of unusual amino acids Ahoda and (2 R ,4 S )‐MePro. A 3D model for cyclopeptide inhibitor interaction with the HDAC active site (see picture) highlights the differences between the binding mode of small‐molecule and cyclopeptide inhibitors.