Lecture on Amino Acids, Peptides, and Proteins

Introduction & Housekeeping

• Delay in getting correct quizzes.
• Quizzes will be distributed at the end of the lecture.

Focus for Today

• Discuss Chapter 28: Amino Acids, Peptides, and Proteins
• Will focus on amino acids and peptides from the synthetic chemistry perspective.

Overview of Biomolecules

• Main classes: Sugars, Proteins, Nucleic Acids, Lipids, Secondary Metabolites

Amino Acids

• Simplest structure: Alanine (archetype for amino acids)
  • Alpha position amino group, smallest with a side chain.
  • Amino acids have amino groups and carboxy groups; linked to form peptides.
• Peptides: Small collections of amino acids (up to 40), larger ones are polypeptides/proteins.

Structure of a Tripeptide

• Example: Phenylalanine, Isoleucine, Leucine
• Naming: Phenylalanyl-Isoleucine-Leucine
• Polypeptides: Long chains that fold, known as proteins.

Polypeptide Examples

• Oxytocin: 9 amino acids, synthesized by Vincent du Vigneaud (Nobel Prize 1955)
  • Involved in uterine contractions, lactation, and emotions/pair bonding.
  • Contains disulfide bonds (Cys-Cys linkages).
• HIV-1 Protease: 99 amino acids, synthesized, used to discover drugs.

Common Naturally Occurring Amino Acids

• 20 amino acids, coded for in body's proteins.
• Categories:
  • Nonpolar Side Chains: E.g., Alanine, Valine, Phenylalanine, Leucine
  • Polar, Uncharged Side Chains: E.g., Serine, Cysteine
  • Acidic Side Chains: E.g., Glutamic Acid
  • Basic Side Chains: E.g., Lysine, Arginine
• Importance of side chains in protein folding, hydrophobic interactions.

Synthesis of Peptides & Proteins

• Difficulty in achieving specificity when combining amino acids.
• Need for protecting groups to control reactions.
  • Examples: Boc group for amino group protection, Benzyl (Bzl) group for carboxyl group.

Peptide Bond Formation

• Amid bond formed between carboxyl group of one amino acid and the amino group of another.
• Use of coupling agents like DCC (Dicyclohexylcarbodiimide) to activate carboxyl group.
  • Side reaction can cause epimerization.
  • Protecting groups strategy reduces unwanted reactions.

Solid Phase Peptide Synthesis (SPPS)

• Invented by Bruce Merrifield (Nobel Prize 1984)
• Process:
  1. Attach amino acid to solid support (polystyrene resin).
  2. Deprotect amino terminus using an acid (e.g., TFA).
  3. Couple next amino acid using DCC.
  4. Repeat process to elongate peptide chain.
  5. Final cleavage from resin using strong acid.

Types of Protecting Groups

• Boc Group: Acid-labile, removed by TFA.
• Benzyl Group: Removed by hydrogenolysis or strong acids.
• Fmoc Group: Base-labile, removed by piperidine.

Advances in SPPS

• Using strong acid like TFA for final removal from the resin.
• Wang Resin: Base-labile linker allowing for Fmoc strategy.

Conclusion

• Significant progress in peptide and protein synthesis aids in biological studies and drug development.

Remaining Work

• Distribute quizzes and finish up writing for review.