Biomolecules: Carbohydrates, Proteins & Nucleic Acids

Derivation — Step-by-Step Mechanism: Peptide Bond Formation & Zwitterion Behavior

1. 1
   $$\text{H}_2\text{N}-\text{CH(R)}-\text{COOH} \rightleftharpoons ^+\text{H}_3\text{N}-\text{CH(R)}-\text{COO}^-$$

   Intramolecular proton transfer from the carboxyl group to the amino group creates a dipolar zwitterion with no net charge at the isoelectric point (pI).

2. 2
   $$\text{R}_1-\text{COOH} + \text{H}_2\text{N}-\text{R}_2 \xrightarrow{-\text{H}_2\text{O}} \text{R}_1-\text{C}(=\text{O})-\text{NH}-\text{R}_2$$

   Nucleophilic attack of the amine on the carboxyl carbon eliminates water to form an amide linkage (peptide bond).

3. 3
   $$[-\text{C}(=\text{O})-\text{NH}- \longleftrightarrow -\text{C}(\text{O}^-)=\text{N}^+\text{H}-]$$

   Resonance delocalization gives the C-N bond ~40% double-bond character, making the peptide unit rigid and planar.

4. 4
   $$\text{Native Protein (Folded)} \xrightarrow{\Delta \text{ or pH change}} \text{Random Coil (Loss of Biological Activity)}$$

   Heat breaks secondary and tertiary hydrogen bonds and hydrophobic interactions without cleaving covalent primary peptide bonds.