Polypeptides
1. Definition
A polypeptide is a linear chain of amino acids linked together by peptide bonds. These chains
are the foundational building blocks of proteins, which are formed when one or more
polypeptides fold into specific 3D structures. Polypeptides can range in length from a few amino
acids (short peptides) to thousands (large proteins).
2. Structure
Amino Acid Structure: Each amino acid has:
- An amino group (-NH₂)
- A carboxyl group (-COOH)
- A unique side chain (R-group) (e.g., hydrophobic, hydrophilic, acidic, or basic).
Peptide Bond: Formed via dehydration synthesis between the carboxyl group of one amino acid
and the amino group of another. This releases a water molecule.
3. Formation
Polypeptides are synthesized through:
Ribosomal Translation:
mRNA is "read" by ribosomes.
Transfer RNA (tRNA) delivers amino acids in sequence.
Peptide bonds form in three stages: initiation,elongation, and termination.
Post-Translational Modifications: After synthesis, polypeptides may undergo changes (e.g.,
phosphorylation, glycosylation) to become functional.
4. Functions
Polypeptides serve diverse roles in biology:
Enzymes: Catalyze biochemical reactions (e.g., amylase breaks down starch).
Hormones: Regulate bodily processes (e.g., **insulin** regulates blood sugar).
Structural Proteins: Provide support (e.g., keratin in hair/nails, collagen in skin).
Antibodies: Part of the immune system.
Transporters: Carry molecules (e.g., hemoglobin transports oxygen).
Antimicrobial Peptides: Fight pathogens ([Link]).
5. Polypeptide vs. Protein
Polypeptide: A single chain of amino acids (may or may not be functional alone).
Protein: A functional molecule composed of one or more polypeptides folded into a specific 3D
structure.
Example: Hemoglobin(4 polypeptide subunits).
6. Key Examples
Short Polypeptides:
Oxytocin(9 amino acids): Regulates social bonding and childbirth.
Glucagon (29 amino acids): Raises blood sugar.
Long Polypeptides/Proteins:
Titin(~34,000 amino acids): Largest known human protein, found in muscles.
7. Applications
Medicine: Synthetic polypeptides are used in drugs (e.g., **insulin analogs** for diabetes).
Biotechnology: Engineered polypeptides for drug delivery or vaccines.
Research: Studying polypeptide folding helps understand diseases like Alzheimer’s (caused by
misfolded proteins).
8. Disorders Linked to Polypeptides
Cystic Fibrosis: Caused by a defective CFTR protein (a polypeptide).
Sickle Cell Anemia: Results from a single amino acid substitution in hemoglobin.
9. Artificial Synthesis
Polypeptides can be synthesized in labs using techniques like **solid-phase peptide synthesis
(SPPS)**, enabling custom designs for research or therapeutics.
Primary, Secondary, and Tertiary Structures of Proteins
Proteins have four levels of structural organization, which determine their shape and function.
We focus on the primary, secondary, and tertiary structures (the fourth, quaternary structure,
applies only to multi-subunit proteins like hemoglobin).
1. Primary Structure
Definition: The linear sequence of amino acids in a polypeptide chain, held together by peptide
bonds.
Determined by: Genetic code (DNA → mRNA → polypeptide).
Example
Insulin’s primary structure is a specific sequence of 51 amino acids.
Importance:
A single amino acid change (mutation) can disrupt protein function (e.g., sickle cell
anemia:glutamate → valine in hemoglobin).
2. Secondary Structure
Definition: Local folding of the polypeptide chain into repeating patterns stabilized by hydrogen
bonds between backbone atoms (not side chains).
Two Major Types:
α-Helix:
Coiled, spring-like structure (right-handed helix).
Stabilized by hydrogen bonds between C=O of one amino acid and N-H of another 4 residues
away.
Example: Keratin (hair, nails), myoglobin.
β-Sheet (Pleated Sheet): Zigzag, sheet-like structure (parallel or antiparallel).
Stabilized by hydrogen bonds between adjacent strands.
Example: Silk fibroin, amyloid fibrils (in Alzheimer’s disease).
Other Elements:
β-Turns (sharp bends) and random coils (unstructured regions).
3. Tertiary Structure
Definition: The 3D folded shape of a single polypeptide chain, stabilized by interactions between
R-groups (side chains).
Stabilizing Forces:
Hydrogen bond (e.g., between serine and glutamate).
Ionic bonds (between charged R-groups, e.g., lysine (+) and aspartate (-)).
Hydrophobic interactions (nonpolar side chains cluster inside the protein).
Disulfide bonds (covalent S-S bonds between cysteine residues).
Van der Waals forces (weak attractions between atoms).
Example:
Myoglobin (oxygen storage in muscles) has a compact, globular tertiary structure.
Enzymes (e.g., lysozyme) have active sites formed by tertiary folding.
Importance:
Misfolding can lead to diseases like Alzheimer’s (amyloid plaques) or Parkinson’s (α-synuclein
aggregates).
Summary
Polypeptides are essential to life, acting as versatile molecules that drive biological processes.
Their sequence, length, and folding determine their ultimate function as part of proteins or
standalone entities. Understanding polypeptides is key to fields like biochemistry, medicine, and
genetic engineering.
