Reagentless Oxidative Folding of Disulfide-Rich Peptides Catalyzed by an Intramolecular Diselenide

Authors

  • Andrew M. Steiner,

    1. Department of Medicinal Chemistry, University of Utah, 421 Wakara Way, Suite 360, Salt Lake City, UT 84108 (USA)
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  • Prof. Dr. Kenneth J. Woycechowsky,

    1. Department of Chemistry, University of Utah, 315 S. 1400 E., Rm. 1320, Salt Lake City, UT 84112 (USA)
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  • Prof. Dr. Baldomero M. Olivera,

    1. Department of Biology, University of Utah, 257 S. 1400 E., Rm. 115, Salt Lake City, UT 84112 (USA)
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  • Prof. Dr. Grzegorz Bulaj

    Corresponding author
    1. Department of Medicinal Chemistry, University of Utah, 421 Wakara Way, Suite 360, Salt Lake City, UT 84108 (USA)
    • Department of Medicinal Chemistry, University of Utah, 421 Wakara Way, Suite 360, Salt Lake City, UT 84108 (USA)
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  • We thank Professors David Blair, David Goldenberg, and Donald Hilvert for helpful discussions and comments on the manuscript. We also acknowledge the assistance of the Peptide Synthesis and Mass Spectrometry Core Facilities at the University of Utah. This work was supported by the NIH Program Project Grant GM 48677.

Abstract

original image

Building bridges: In cysteine-rich peptides, diselenides can be used as a proxy for disulfide bridges as the energetic preference for Se[BOND]Se bonds over mixed Se[BOND]S bonds simplifies folding (see picture). An intramolecular diselenide bond efficiently catalyzes the oxidative folding of selenopeptide analogues of conotoxins, and serves as a reagentless method to accelerate formation of various native disulfide bridging patterns.

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