Abstract
We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(π)-position of a key histidine residue in phosphothreonine-containing peptides can impart high binding affinity against the polo-box domain of polo-like kinase 1. Our current paper investigates the mechanism leading to this N(π)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(π)-modified peptides. These agents represent new and potentially important tools for biological studies.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Alkylation
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Cell Cycle Proteins / chemical synthesis*
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Cell Cycle Proteins / chemistry
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Electrons
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Histidine / analogs & derivatives
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Histidine / chemical synthesis*
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Histidine / chemistry*
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Imidazoles / chemistry*
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Molecular Structure
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Peptides / chemical synthesis*
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Peptides / chemistry*
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Phosphothreonine / chemical synthesis*
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Phosphothreonine / chemistry*
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Polo-Like Kinase 1
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Protein Binding
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Protein Serine-Threonine Kinases / chemical synthesis*
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Protein Serine-Threonine Kinases / chemistry
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Proto-Oncogene Proteins / chemical synthesis*
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Proto-Oncogene Proteins / chemistry
Substances
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Cell Cycle Proteins
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Imidazoles
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Peptides
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Proto-Oncogene Proteins
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Phosphothreonine
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Histidine
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Protein Serine-Threonine Kinases