Peptide Bond Formation and Hydrolysis

Formation (condensation reaction):

$\text{H}_2\text{N-CHR}_1\text{-COOH} + \text{H}_2\text{N-CHR}_2\text{-COOH} \xrightarrow{-\text{H}_2\text{O}} \text{H}_2\text{N-CHR}_1\text{-CO-NH-CHR}_2\text{-COOH}$

• One $H_{2}O$ lost per peptide bond formed
• For n amino acids: (n-1) peptide bonds, (n-1) $H_{2}O$ released

Hydrolysis (reverse, requires $H_{2}O$ + catalyst):

$\text{peptide} + \text{H}_2\text{O} \xrightarrow{\text{H}^+/\text{OH}^-/\text{enzyme}} \text{amino acids}$

Geometry of the peptide bond:

The peptide bond has ~40% double-bond character due to resonance:

$-\text{C}(=\text{O})-\text{NH}- \leftrightarrow -\text{C}(-\text{O}^-) = \overset{+}{\text{N}}\text{H}-$

Consequences:

1. Planarity: All six atoms of the peptide unit (Cα-CO-NH-Cα) lie in one plane
2. Trans preference: R groups on adjacent Cα atoms prefer the trans (anti) arrangement (~99.9%)
3. Restricted rotation: Around C-N bond (barrier ~88 kJ/mol), not freely rotatable
4. Partial ionic character: ~40% contribution from the charged resonance form

NEET counting rule:

• Dipeptide: 1 peptide bond, 1 $H_{2}O$ released
• Tripeptide: 2 peptide bonds, 2 $H_{2}O$ released
• Polypeptide with n residues: (n-1) bonds, (n-1) $H_{2}O$

SMILES for Gly-Ala (glycylalanine): NCC(=O)N[C@@H](C)C(=O)O