Abstract
Natural analogues (D, C2, and VII) of actinomycin inhibit Grb2 SH2 domain binding with phosphopeptide-derived from Shc in vitro and in intracellular system. To study structure-activity relationships, 13 actinomycin analogues were synthesized and we found that the inhibition activity depended on the substituents of cyclic peptide groups in actinomycin and two analogues with Tyr residue are the most potent inhibitors with IC50 value of 0.5 and 0.8 microM, respectively.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Amino Acid Substitution
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Animals
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / pharmacology*
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Biological Assay
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Cell Line, Transformed
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Dactinomycin / analogs & derivatives*
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Dactinomycin / chemistry
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Dactinomycin / pharmacology*
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GRB2 Adaptor Protein
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Growth Inhibitors / pharmacology
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Humans
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Immunoblotting
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Molecular Structure
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Precipitin Tests
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Protein Binding
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Proteins / metabolism*
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Recombinant Fusion Proteins / metabolism
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Structure-Activity Relationship
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src Homology Domains*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Antibiotics, Antineoplastic
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GRB2 Adaptor Protein
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GRB2 protein, human
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Growth Inhibitors
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Proteins
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Recombinant Fusion Proteins
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SHC1 protein, human
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Dactinomycin