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Fluoroolefin Isosteres

  • Protocol
Peptidomimetics Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 23))

Abstract

Replacement of the amide bond in the peptide backbone can improve the activity, stability, or bioavailability of the resultant unnatural peptide (1). Amide bond surrogates cannot only impart peptidase resistance, but can also facilitate conformational control of the target peptide. Although the alkene ψ[C=C] isostere is an accurate mimic of the steric demand, bond lengths, and bond angles of the amide bond (2–6), it also permits construction of both the (E) and (Z) cis- and trans-) isomers independently. Unlike the amide bond, which has some degree of flexibility, the ψ[C=C] isostere is conformational fixed (7–8). The ψ[CF=C] isostere retains these attributes, but accurately mimics the electronic features of the amide bond (9–11) to include dipole moment, charge distribution, and electrostatic potential.

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Author information

Authors and Affiliations

  1. Department of Chemistry, State University of New York, Albany, New York

    J. T. Welch & T. Allmendinger

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  1. J. T. Welch
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  2. T. Allmendinger
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  1. Glaxo Wellcome., Inc., Research Triangle Park, NC

    Wieslaw M. Kazmierski

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© 1999 Humana Press Inc., Totowa, NJ

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Welch, J.T., Allmendinger, T. (1999). Fluoroolefin Isosteres. In: Kazmierski, W.M. (eds) Peptidomimetics Protocols. Methods in Molecular Medicine™, vol 23. Humana Press. https://doi.org/10.1385/0-89603-517-4:357

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  • DOI: https://doi.org/10.1385/0-89603-517-4:357

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-517-1

  • Online ISBN: 978-1-59259-605-8

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