Peptide Bond Chemistry
Understanding the amide bond that links amino acids: resonance, planar geometry, and the Ramachandran plot.
What Is a Peptide Bond?
A peptide bond is the covalent amide linkage formed between the carboxyl group of one amino acid and the amino group of another. This bond is created through a dehydration synthesis (condensation) reaction, where one molecule of water is released for each bond formed.
The general reaction proceeds as follows: the nitrogen of the incoming amino acid attacks the carbonyl carbon of the first amino acid, displacing a hydroxyl group and forming an amide bond. This reaction is thermodynamically unfavorable under standard conditions and requires energy input, typically supplied by ATP in biological systems.
Resonance and Partial Double Bond Character
The peptide bond is not a simple single bond. Due to resonance, the lone pair of electrons on the nitrogen atom delocalizes into the adjacent carbonyl group. This gives the peptide bond approximately 40% double bond character.
This partial double bond character has critical consequences:
- The C-N bond cannot rotate freely (bond length ~1.32 A, shorter than a typical C-N single bond of ~1.49 A)
- The C=O bond is slightly elongated (~1.24 A vs ~1.21 A in isolated carbonyls)
- The six atoms involved in the peptide bond (C-alpha, C=O, N-H, and the next C-alpha) are constrained to a planar geometry
Trans vs Cis Configuration
Because rotation about the peptide bond is restricted, the two alpha-carbons can be positioned on the same side (cis) or opposite sides (trans) of the peptide bond. The trans configuration is strongly favored in nature (~99.6% of peptide bonds) because it minimizes steric clashes between side chains.
Proline is the exception: its cyclic side chain bonds back to the nitrogen, reducing the energy difference between cis and trans forms. Roughly 6% of X-Pro bonds adopt the cis configuration.
The Ramachandran Plot
The Ramachandran plot maps the two allowable torsion angles in a peptide backbone:
- Phi (phi): rotation about the N-C(alpha) bond
- Psi (psi): rotation about the C(alpha)-C bond
Most combinations of phi and psi angles are sterically forbidden. Allowed regions correspond to common secondary structures:
- Alpha-helix: phi ~ -60, psi ~ -45
- Beta-sheet: phi ~ -120 to -140, psi ~ +110 to +135
- Left-handed helix: phi ~ +60, psi ~ +45
Mnemonic
“Peptide = Planar + Partial-double” — the two P-words capture the defining features of the peptide bond: it is flat and it has partial double bond character.
Summary
| Feature | Detail |
|---|---|
| Bond type | Amide (C(=O)-NH) |
| Reaction | Dehydration synthesis |
| Bond character | ~40% double bond (resonance) |
| Preferred configuration | Trans |
| Torsion angles | Phi (phi) and Psi (psi) |
| Plot | Ramachandran plot |