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. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.
Peri, F., Airoldi, C., Colombo, S., Martegani, E., van Neuren, A., Stein, M., et al. (2005). Design, synthesis and biological evaluation of sugar-derived Ras inhibitors. CHEMBIOCHEM, 6(10), 1839-1848 [10.1002/cbic.200400420].
Design, synthesis and biological evaluation of sugar-derived Ras inhibitors
PERI, FRANCESCO;AIROLDI, CRISTINA;COLOMBO, SONIA;MARTEGANI, ENZO;NICOTRA, FRANCESCO
2005
Abstract
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. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.
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