Bending Rigid Molecular Rods: Formation of Oligoproline Macrocycles

Authors

  • Dr. Conor C. G. Scully,

    1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
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  • Dr. Vishal Rai,

    1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
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  • Dr. Gennadiy Poda,

    1. Medicinal Chemistry Platform, Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College Street, Toronto, Ontario, M5G 0A3 (Canada)
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  • Serge Zaretsky,

    1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
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  • Dr. Darcy C. Burns,

    1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
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  • Dr. R. Scott Houliston,

    1. Ontario Cancer Institute, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7 (Canada)
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  • Tiantong Lou,

    1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
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  • Prof. Dr. Andrei K. Yudin

    Corresponding author
    1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
    • Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
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Abstract

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Bent but not broken: Cyclic oligoprolines are accessed in a reaction that effectively bends rigid oligoproline peptides (see scheme; TBDMS=tert-butyldimethylsilyl). The stitching is accomplished during macrocyclization enabled by aziridine aldehydes and isocyanides. Molecular modeling studies suggest that electrostatic attraction between the termini of the linear peptide is pivotal for macrocyclization. The macrocycles were studied by circular dichroism with a polyproline II structure being observed in larger macrocycles.

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