Abstract
Many proteins are transported from the nucleus to the cytoplasm by the exportin CRM1, which recognizes cargo proteins through a leucine rich nuclear export signal (NES). This nuclear export process can be inhibited by several small molecules, both natural products and fully synthetic compounds. The structural basis for the inhibition of nuclear export by leptomycin (LMB) based on disruption of the protein/protein interaction between CRM1 and cargo proteins is discussed. The chemistry and inhibition of nucleocytoplasmic transport of leptomycin, anguinomycin and derivatives, goniothalamin, JBIR-02, valtrate, dihydrovaltrate, ACA, peumusolide A and several synthetic compounds are presented. Consequences for the design of nuclear export inhibitors are discussed, and the potential of these compounds as anticancer agents is evaluated.
Keywords: Nuclear export, natural products, chemical biology, anticancer compounds, cell biology, biopolymers, chemical genetics, protein/protein interaction, chemical inteference, phenotypes
Current Drug Targets
Title: Controlling Protein Transport by Small Molecules
Volume: 12 Issue: 11
Author(s): Karl Gademann
Affiliation:
Keywords: Nuclear export, natural products, chemical biology, anticancer compounds, cell biology, biopolymers, chemical genetics, protein/protein interaction, chemical inteference, phenotypes
Abstract: Many proteins are transported from the nucleus to the cytoplasm by the exportin CRM1, which recognizes cargo proteins through a leucine rich nuclear export signal (NES). This nuclear export process can be inhibited by several small molecules, both natural products and fully synthetic compounds. The structural basis for the inhibition of nuclear export by leptomycin (LMB) based on disruption of the protein/protein interaction between CRM1 and cargo proteins is discussed. The chemistry and inhibition of nucleocytoplasmic transport of leptomycin, anguinomycin and derivatives, goniothalamin, JBIR-02, valtrate, dihydrovaltrate, ACA, peumusolide A and several synthetic compounds are presented. Consequences for the design of nuclear export inhibitors are discussed, and the potential of these compounds as anticancer agents is evaluated.
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Cite this article as:
Gademann Karl, Controlling Protein Transport by Small Molecules, Current Drug Targets 2011; 12 (11) . https://dx.doi.org/10.2174/138945011798109446
DOI https://dx.doi.org/10.2174/138945011798109446 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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