The ras pathway modulator melophlin a targets dynamins
| Autor: | Knoth, Tanja, Warburg, Karin, Katzka, Catherine, Rai, Amrita, Wolf, Alexander, Brockmeyer, Andreas, Janning, Petra, Reubold, Thomas F., Eschenburg, Susanne, Manstein, Dietmar J., Hübel, Katja, Kaiser, Markus, Waldmann, Herbert |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Dynamins
Proteomics Stereochemistry Systems biology Computational biology Catalysis Structure-Activity Relationship Alkanes Humans Structure–activity relationship Mode of action Biological Products Molecular Structure Cell growth Chemistry Kinase Biological activity General Medicine General Chemistry Pyrrolidinones Genes ras Mitogen-Activated Protein Kinases Signal transduction Biologie Signal Transduction |
| Popis: | The Ras/mitogen-activated protein (MAP) kinase signal transduction pathway regulates numerous biological programs including cell growth and differentiation, and harbors several important anticancer-drug targets. Recent research, in particular inspired by systems biology approaches, revealed the importance of dynamic spatiotemporal regulation of and interplay between the Ras network members and their interaction with other signaling modules for fully functional Ras signaling. Because of their rapid, conditional, and reversible mode of action, small-molecule modulators of protein function are particularly suitable tools for the conditional analysis of such dynamic biological processes, and hold great promise for the study of biological systems. Therefore, the identification of novel small-molecule modulators of signaling through the Ras network and the identification of their molecular targets are of major interest. 6] The naturally occurring tetramic acids melophlin A and B (1 and 2, Scheme 1A) reverse the morphology of HRas-transformed NIH3T3 fibroblasts at a concentration of 5 mgmL 1 (that is, IC50= 14 mm). [7] However, the biological targets of the melophlins and their link to the Ras network have not been identified. Herein, we report the synthesis of a melophlin-inspired compound collection and a subsequent chemical proteomics investigation, which revealed that melo |
| Databáze: | OpenAIRE |
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