Peptides

Introduction to Biochemistry

Course Information

• Course Title: CHEM 2713

• Instructor: Dr. Amitabh Jha

• Institution: Acadia University

Amino Acids, Peptides, and Proteins

Definitions

• Amino Acid:
    - Monomer unit of proteins.
    - Legacy Definition: Building blocks of peptides and proteins.

• Peptide:
    - A molecule that consists of 2 to 50 amino acids.
    - Types of Peptides:
      - Oligopeptides:
        - Composed of 2 to 20 amino acids.
      - Polypeptides:
        - Composed of 20 to 50 amino acids.
    - Tend to be less well defined structurally than proteins.

• Protein:
    - A macromolecule made up of 50 or more amino acids.
    - Comprised of one or more polypeptides.
    - Capable of adopting complex conformations:
      - Secondary Structure
      - Tertiary Structure
      - Quaternary Structure
    - Functions include:
      - Catalysis
      - Metabolic regulation
      - Transport
      - Defense
      - Structural roles in organisms

Structural Comparison

• Peptides and proteins are structurally similar:
    - Both consist of chains of amino acids.
    - Held together by peptide bonds (also called amide bonds).

Peptide Bond Formation

Chemical Reactions of Amino Acids

• Amino acids participate in numerous chemical reactions due to their functional groups (carboxyl, amino, R groups).

• Peptide Bond Formation:
    - Peptide bonds link amino acids through nucleophilic acyl substitution.
    - It's a dehydration reaction, resulting in the release of a water molecule.
    - Example: Reaction of two amino acids results in the formation of a dipeptide.

Mechanism of Peptide Bond Formation

• Nucleophilic Acyl Substitution:
    - Nucleophile attacks the carbonyl carbon of an amino acid.
    - Formation of a tetrahedral intermediate, stabilizing the reaction.

• Addition-Elimination Mechanism:
    - Nucleophilic attack followed by the elimination of a leaving group.

Structural Characteristics of Peptide Bonds

• The peptide bond is rigid and flat.
    - Linus Pauling (1954) characterized this rigidity.

• C-N Bonds:
    - Shorter than typical C-N bonds, exhibiting partial double-bond characteristics due to resonance.
    - This rigidity limits the rotation of one-third of the bonds in a polypeptide backbone, constraining its conformational possibilities.

Disulfide Bridges

• Formation of Disulfide Bridges:
    - Occurs via the oxidation of two cysteine residues, resulting in a disulfide bond (cystine).
    - Stabilizes the structure of proteins and polypeptides.

Functions of Peptides

Biological Importance of Peptides

• Despite being less complex than proteins, peptides exhibit vital biological functions.

• Examples of Biologically Important Peptides:
    - Glutathione:
      - A tripeptide vital for protein and DNA synthesis, metabolism of toxic substances, and amino acid transport.
    - Vasopressin:
      - Antidiuretic hormone regulating water balance, appetite, and body temperature.
    - Oxytocin:
      - Involved in uterine contractions and lactation.

Titration of Amino Acids

Tripeptide Titration

• Calculating the isoelectric point (pI) of a tripeptide involves determining the pKa values of the acidic (
  ) and basic (
  ) groups.

• Formula for calculating pI:
    - $pI = rac{1}{2}(pK_1 + pK_2)$

Example Calculations

• For Glycine:
    - $pK_1 = 2.34$
    - $pK_2 = 9.60$

• For Valine:
    - $pK = 9.62$

• For Alanine:
    - $pK_1 = 2.34$

Amino Acid Properties

Properties Table

• Key Properties and Conventions:
    - Hydropathy Index: A measure of the tendency of an amino acid to seek an aqueous or hydrophobic environment; negative values indicate hydrophilicity while positive values indicate hydrophobicity.

• Example amino acids and their properties include:
    - Glycine (Gly, G):
      - pKa values: $pK_1 = 2.34$, $pK_2 = 9.60$, $pI = 5.97$, Hydropathy index = -0.4
      - Occurrence in proteins: 7.2%.
    - Alanine (Ala, A):
      - pKa values: $pK_1 = 2.34$, $pK_2 = 9.69$, $pI = 6.01$, Hydropathy index = 1.8
      - Occurrence in proteins: 7.8%.
    - More amino acids with specific characteristics are detailed in corresponding tables.

Conclusion

Questions

• Students are encouraged to ask questions to clarify their understanding of the material covered, especially regarding titration calculations and properties of amino acids.