Lecture Notes: Peptide Bond Formation and Cleavage

Introduction

• Proteins are formed from folded polypeptide chains.
• Polypeptide chains are formed by linking amino acids via peptide bonds.

Structure of Amino Acids

• Backbone: Amino group, carboxylic acid group, alpha carbon, and side chain (R).
• Peptide Bond Formation: Involves nucleophilic addition-elimination between carboxyl group of one amino acid and amino group of another.
  • Electron pair on amino group forms bond with carbonyl carbon.
  • Water molecule is released.
  • Result is a new dipeptide with a peptide bond.

Characteristics of Peptide Bonds

• Peptide bond is an amide bond between two amino acids.
• Rigid and Planar: Stabilized by resonance delocalization of electrons from nitrogen to carbonyl oxygen.
  • Peptide bond has double-bond character, making it rigid and planar.
  • Free Rotation is possible around alpha carbon atoms, despite rigidity around the peptide bond itself.

Formation of Polypeptide Chains

• Adding amino acids repeats a pattern in the backbone: Nitrogen atom, alpha carbon, carbonyl carbon.
• Polypeptide Chain Terminology:
  • N-terminal: Starts with a nitrogen atom.
  • C-terminal: Ends with a carbonyl carbon.
  • Residue: Each amino acid within a chain.

Cleavage of Peptide Bonds

• Hydrolysis: Process to break peptide bonds into amino acids.
  • Acid Hydrolysis: Nonspecific cleavage using strong acids and heat.
  • Proteolysis: Specific cleavage using proteases (enzymes).
    • Example: Trypsin cleaves on the carboxyl side of basic amino acids (arginine and lysine).
    • Trypsin is produced by the pancreas to aid in digestion.

Specific Proteolysis

• Trypsin cleaves at specific sites on the polypeptide chain.
  • Cleaves on C-terminal of arginine and lysine.
  • Results in specific fragments post-cleavage.
• Importance of understanding that proteases are specific, unlike nonspecific acid hydrolysis.

Conclusion

• Understanding these processes is crucial for grasping how proteins are formed and broken down.
• Memorization of specific proteases may not be necessary, but understanding their specificity is important.