Amino Acids, Peptides, and Proteins

Announcements

• Johnny and Kim xeroxed the wrong quiz, so the correct one will be distributed at the end of the lecture.

Key Biomolecules

• Main classes of biomolecules: sugars, proteins, nucleic acids, lipids, secondary metabolites (e.g., alkaloids).
• Chapter 28 focuses on amino acids, peptides, and proteins, particularly from the perspective of synthetic chemistry.

Amino Acids

• Simplest structure is alanine (an alpha-amino acid).
  • Amino acids can have amino groups (NH2) and carboxyl groups (COOH).
  • Amino acids link end-to-end to form peptides (≤40 amino acids) and proteins (>40 amino acids).
  • Poly-peptides: often have folded structures and biological origins.
• Examples
  • Tripeptide: phenylalanine, isoleucine, leucine.
  • Terminology: e.g., phenylalanylisoleucine.
• Structure and properties
  • Oxytocin: nona-peptide (9 amino acids) with a disulfide bond linked between cysteine residues.
  • Biological properties: linked to uterine contractions, lactation, emotions, and pair bonding.

Chemical Synthesis of Peptides and Proteins

• Importance: Allows understanding biological functions by synthesizing effect-mimicking molecules.
• Synthesis Strategy: Protecting groups are used to selectively protect amino and carboxyl groups to control the synthesis of the target peptide.
  • Coupling agents (e.g., DCC) activate carboxyl groups to react with amino groups forming amides.
• Example: Synthesis of dipeptide
  • Protect amino group (e.g., with TBDMS ether) and carboxyl group (e.g., as an ester).
  • Use DCC to activate carboxyl groups for coupling with amino groups.

Modern Solid Phase Peptide Synthesis (SPPS)

• Innovation by Bruce Merrifield (1960s)
  • Polymer beads for supporting polypeptide synthesis.
  • Nobel Prize in 1984.
• Procedure
  1. Attach first amino acid to resin via its carboxyl group.
  2. De-protect N-terminus.
  3. Couple next amino acid (protected N-terminus) using DCC.
  4. Repeat for desired peptide length.
  5. Cleave and de-protect final peptide from resin (e.g., using acids like TFA).
• Protecting Groups
  • Fmoc (base labile) and Boc (acid labile) groups are common.
  • Fmoc can be removed using pyridine.
  • Boc is often used with TFA for removal.

Structural Features of Amino Acids

• Non-polar: Alanine (methyl group), Phenylalanine (benzyl group), Valine (isopropyl group), Leucine (isobutyl group).
  • Hydrophobic interactions are significant in protein folding.
• Polar: Serine (hydroxyl group), Cysteine (thiol group), Glutamic acid (carboxyl group), Glutamine (amide group), Lysine (amine group), Arginine (guanidinium group).
• Special Cases: Proline (imino acid, secondary amine), Glycine (no side chain, achiral), Cysteine (R stereochemistry due to sulfur's priority).

Summary

• The chapter covers the chemical synthesis of amino acids, peptides, and proteins, emphasizing protecting groups and coupling agents.
• Modern peptide synthesis (e.g., SPPS) has revolutionized the field, enabling the synthesis of both peptides and small proteins in the lab.
• Understanding the structure and properties of amino acids aids in the design and synthesis of peptides with desired biological functions.