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Investigation of unanticipated alkylation at the N(?) position of a histidyl residue under Mitsunobu conditions and synthesis of orthogonally protected histidine analogues.

ABSTRACT: We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(?)-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(?)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(?)-modified peptides. These agents represent new and potentially important tools for biological studies.

SUBMITTER: Qian W

PROVIDER: S-EPMC3211136 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Investigation of unanticipated alkylation at the N(π) position of a histidyl residue under Mitsunobu conditions and synthesis of orthogonally protected histidine analogues.

Qian Wenjian W Liu Fa F Burke Terrence R TR

The Journal of organic chemistry 20111003 21

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 import ...[more]

PMID: 21950469

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