Structure-activity relationship of isoform selective inhibitors of Rac1/1b GTPase nucleotide binding
| Autor: | Thierry Taverne, Rachel Carton, Bertrand Leblond, Laurent Desire, Diego Pallares, Laure Pognante, Fabien Schweighoffer, Cedric Chauvignac, Eric Beausoleil, Sandrine Lacombe, Nathalie Lambeng, Séverine Coutadeur, Hélène Peillon, Florence Bachelot, Catherine De Oliveira, Virginie Picard |
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| Rok vydání: | 2009 |
| Předmět: |
rac1 GTP-Binding Protein
Berberine G protein Clinical Biochemistry Pharmaceutical Science RAC1 GTPase Plasma protein binding CDC42 Biochemistry Structure-Activity Relationship Drug Discovery Structure–activity relationship Protein Isoforms Nucleotide Computer Simulation Amino Acid Sequence Binding site Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Binding Sites Chemistry Nucleotides Organic Chemistry Isoquinolines Molecular Medicine Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry letters. 19(19) |
| ISSN: | 1464-3405 |
| Popis: | The synthesis of a series of berberine, phenantridine and isoquinoline derivatives was realized to explore their Rho GTPase nucleotide inhibitory activity. The compounds were evaluated in a nucleotide binding competition assay against Rac1, Rac1b, Cdc42 and in a cellular Rac GTPase activation assay. The insertion of 19 AA in the splice variant Rac1b is shown to be sufficient to introduce a conformational difference that allows compounds 4, 21, 22, and 26 to exhibit selective inhibition of Rac 1b over Rac1. |
| Databáze: | OpenAIRE |
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