An evaluation of peptide-bond isosteres

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alkenes / chemistry*
  • Amino Acid Sequence
  • Carbohydrate Biochemistry / methods*
  • Electrons
  • Esters / chemistry*
  • Fluorides / chemistry
  • Hydrogen Bonding
  • Isomerism
  • Models, Molecular
  • Molecular Mimicry
  • Peptides / chemistry*
  • Protein Conformation
  • Static Electricity
  • Thermodynamics
  • Thioamides / chemistry*


  • Alkenes
  • Esters
  • Peptides
  • Thioamides
  • Fluorides