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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2003-6-11
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pubmed:abstractText |
Development of Grb2-SH2 domain antagonists is an effective approach to inhibit the growth of malignant cells by modulating Grb2-related Ras signaling. We report here potent Grb2-SH2 domain antagonists that do not rely on phosphotyrosine or its mimics. These non-phosphorylated antagonists were developed and further modified by constraining the backbone conformation and optimizing amino acid side chains of a phage library-derived peptide, G1TE. After extensive SAR studies and structural optimization, non-phosphorylated peptide 12 was discovered with an IC(50) of 75 nM. This potent peptidomimetic provides a novel template for the development of non-pTyr containing Grb2-SH2 domain antagonists and acts as a chemotherapeutic lead for the treatment of erbB2-related cancer.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0960-894X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2173-7
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:12798329-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12798329-Amino Acids,
pubmed-meshheading:12798329-Antineoplastic Agents,
pubmed-meshheading:12798329-Binding Sites,
pubmed-meshheading:12798329-Circular Dichroism,
pubmed-meshheading:12798329-Computer Simulation,
pubmed-meshheading:12798329-GRB2 Adaptor Protein,
pubmed-meshheading:12798329-Ligands,
pubmed-meshheading:12798329-Models, Molecular,
pubmed-meshheading:12798329-Molecular Conformation,
pubmed-meshheading:12798329-Molecular Mimicry,
pubmed-meshheading:12798329-Peptide Library,
pubmed-meshheading:12798329-Phosphorylation,
pubmed-meshheading:12798329-Phosphotyrosine,
pubmed-meshheading:12798329-Proteins,
pubmed-meshheading:12798329-Structure-Activity Relationship,
pubmed-meshheading:12798329-src Homology Domains
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pubmed:year |
2003
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pubmed:articleTitle |
Potent Grb2-SH2 domain antagonists not relying on phosphotyrosine mimics.
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pubmed:affiliation |
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, 21702, Frederick, MD, USA.
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pubmed:publicationType |
Journal Article
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