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Review
. 2011 Aug 16;12(12):1801-7.
doi: 10.1002/cbic.201100272. Epub 2011 Jul 12.

An Evaluation of Peptide-Bond Isosteres

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Free PMC article
Review

An Evaluation of Peptide-Bond Isosteres

Amit Choudhary et al. Chembiochem. .
Free PMC article

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.

Figures

Figure 1
Figure 1
(A) Lone pairs of an amide oxygen, and their partial covalent bonds in an α-helix: (B) Hydrogen bond, and (C) nπ* interaction.[9b]
Figure 2
Figure 2
nπ* interaction and n)(π Pauli repulsion in the trans isomer of Xaa–Pro isosteres.[9a]
Scheme 1
Scheme 1
Canonical resonance structures of peptide-bond isosteres.
Scheme 2
Scheme 2
Structure of a peptide bond (center) and some surrogates. This minireview is focused on the four isosteres in the inner circle.
Scheme 3
Scheme 3
Bond lengths (Å) in peptide-bond isosteres.[17]
Scheme 4
Scheme 4
Cis–trans equilibrium of a peptide bond and isosteres.
Scheme 5
Scheme 5
Cis–trans equilibrium of an Xaa–Pro peptide bond and isosteres.[9c]
Scheme 6
Scheme 6
Cis–trans equilibrium of a peptide bond and isosteres in a β-turn.[45]

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