Peptide bond

Resonance forms of the peptide group

The amide group has two secondary structures (such as the α-helix), producing a large net dipole.

The partial double bond character can be strengthened or weakened by modifications that favor one resonance form over another. For example, the double-bonded form is disfavored in nitrogen (See Figure 4.)

Cis/trans isomers of the peptide group

The partial double bond renders the amide group planar, occurring in either the cis or trans isomers. In the unfolded state of proteins, the peptide groups are free to isomerize and adopt both isomers; however, in the folded state, only a single isomer is adopted at each position (with rare exceptions). The trans form is preferred overwhelmingly in most peptide bonds (roughly 1000:1 ratio in trans:cis populations). However, X-Pro peptide groups tend to have a roughly 3:1 ratio, presumably because the symmetry between the C^α and C^δ atoms of proline makes the cis and trans isomers nearly equal in energy (See figure, below).

The catalyzed) by changes that favor the single-bonded form, such as placing the peptide group in a hydrophobic environment or donating a hydrogen bond to the nitrogen atom of an X-Pro peptide group. Both of these mechanisms for lowering the activation energy have been observed in peptidyl prolyl isomerases (PPIases), which are naturally occurring enzymes that catalyze the cis-trans isomerization of X-Pro peptide bonds.

Conformational protein folding is usually much faster (typically 10-100 ms) than cis-trans isomerization (10-100 s). A nonnative isomer of some peptide groups can disrupt the conformational folding significantly, either slowing it or preventing it from even occurring until the native isomer is reached. However, not all peptide groups have the same effect on folding; nonnative isomers of other peptide groups may not affect folding at all.

Chemical reactions

Owing to its resonance stabilization, the peptide bond is relatively unreactive under physiological conditions, even less than similar compounds such as cyclol or, more specifically, a thiacyclol, an oxacyclol or an azacyclol, respectively.

References

• Pauling L. (1960) The Nature of the Chemical Bond, 3rd. ed., Cornell University Press. ISBN 0-8014-0333-2

• Stein RL. (1993) "Mechanism of Enzymatic and Nonenzymatic Prolyl cis-trans Isomerization", Adv. Protein Chem., 44, 1-24.

• Schmid FX, Layr LM, Mücke M and Schönbrunner ER. (1993) "Prolyl Isomerases: Role in Protein Folding", Adv. Protein Chem., 44, 25-66.

• Fischer G. (1994) "Peptidyl-Prolyl cis/trans Isomerases and Their Effectors", Angew. Chem. Int. Ed. Engl., 33, 1415-1436.