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An Evaluation of Peptide-Bond Isosteres

Authors

  • Amit Choudhary,

    1. Graduate Program in Biophysics, University of Wisconsin–Madison, 1525 Linden Drive, Madison, WI 53706-1534 (USA)
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  • Prof. Ronald T. Raines

    Corresponding author
    1. Department of Biochemistry, University of Wisconsin–Madison, 433 Babcock Drive, Madison, WI 53706-1544 (USA)
    2. Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, WI 53706-1322 (USA)
    • Department of Biochemistry, University of Wisconsin–Madison, 433 Babcock Drive, Madison, WI 53706-1544 (USA)
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Abstract

Peptide-bond isosteres can enable a deep interrogation of the structure and function of a peptide or protein by amplifying or attenuating particular chemical properties. In this Minireview, the electronic, structural, and conformational attributes of four such isosteres—thioamides, esters, alkenes, and fluoroalkenes—are examined in detail. In particular, the ability of these isosteres to partake in noncovalent interactions is compared with that of the peptide bond. The consequential perturbations provide a useful tool for chemical biologists to reveal new structure–function relationships, and to endow peptides and proteins with desirable attributes.

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