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Design, Synthesis and Biological Evaluation of Sugar‐Derived Ras Inhibitors
Author(s) -
Peri Francesco,
Airoldi Cristina,
Colombo Sonia,
Martegani Enzo,
van Neuren Anske Stephanie,
Stein Matthias,
Marinzi Chiara,
Nicotra Francesco
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400420
Subject(s) - in vivo , in vitro , chemistry , bicyclic molecule , sugar , biochemistry , arabinose , scaffold , stereochemistry , combinatorial chemistry , cell growth , biology , xylose , medicine , microbiology and biotechnology , fermentation , biomedical engineering
The design and synthesis of novel Ras inhibitors with a bicyclic scaffold derived from the natural sugar D ‐arabinose are presented. Molecular modelling showed that these ligands can bind Ras by accommodating the aromatic moieties and the phenylhydroxylamino group in a cavity near the Switch II region of the protein. All the synthetic compounds were active in inhibiting nucleotide exchange on p21 human Ras in vitro, and two of them selectively inhibited Ras‐dependent cell growth in vivo.