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The Tubulin‐Bound Conformation of Discodermolide Derived by NMR Studies in Solution Supports a Common Pharmacophore Model for Epothilone and Discodermolide
Author(s) -
SánchezPedregal Víctor M.,
Kubicek Karel,
Meiler Jens,
Lyothier Isabelle,
Paterson Ian,
Carlomagno Teresa
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.200602793
Subject(s) - pharmacophore , chemistry , epothilone , stereochemistry , tubulin , ligand (biochemistry) , microtubule , biochemistry , receptor , biology , microbiology and biotechnology
Bound to have similarities : Although the overall shape of discodermolide bound to tubulin resembles the structure of the free ligand, the precise conformation and orientation of the lactone ring are different. A partially overlapping pharmacophore model supported by protein‐mediated interligand NOE signals (see picture) is proposed to explain the similar (but not fully equivalent) biological activity of discodermolide and epothilone A.