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Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation.

ABSTRACT: Photoaffinity labeling is a powerful tool to identify protein targets of biologically active small molecules, yet is often limited by the size, chemical properties, and availability of photoreactive groups. We report an improved synthesis of photo-leucine, a diazirine-based photoreactive analogue of leucine, and demonstrate its incorporation into a cyclodepsipeptide inhibitor of cotranslational translocation. Photoaffinity labeling in a crude membrane fraction, followed by "click chemistry" with a rhodamine-azide reporter, enabled the identification of Sec61alpha, the structural core of the Sec61 translocation channel, as the inhibitor's target.

SUBMITTER: MacKinnon AL

PROVIDER: S-EPMC2574519 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation.

MacKinnon Andrew L AL Garrison Jennifer L JL Hegde Ramanujan S RS Taunton Jack J

Journal of the American Chemical Society 20071106 47

Photoaffinity labeling is a powerful tool to identify protein targets of biologically active small molecules, yet is often limited by the size, chemical properties, and availability of photoreactive groups. We report an improved synthesis of photo-leucine, a diazirine-based photoreactive analogue of leucine, and demonstrate its incorporation into a cyclodepsipeptide inhibitor of cotranslational translocation. Photoaffinity labeling in a crude membrane fraction, followed by "click chemistry" with ...[more]

PMID: 17983236

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