Peptide Bonds &
Protein Primary Structure
Master the covalent backbone of proteins: how amino acids link via dehydration synthesis, and why the linear sequence defines function.
The Building Blocks: Amino Acids
Proteins are polymers built from 20 standard amino acids. Each amino acid shares a common core structure but differs in its R group (side chain), which determines its chemical properties.
Forming the Bond: Dehydration Synthesis
A peptide bond forms when the carboxyl group of one amino acid reacts with the amino group of another, releasing one molecule of water. This is a condensation reaction.
Peptide Bond Character
Resonance and Rigidity
The nitrogen's lone pair delocalizes into the carbonyl, creating a resonance hybrid. This gives the \(\text{C-N}\) bond ~40% double-bond character, making the peptide bond rigid and planar.
Backbone Rotation: \(\phi\) and \(\psi\) Angles
What Is Primary Structure?
The primary structure of a protein is the linear sequence of amino acids from the N-terminus to the C-terminus, connected by peptide bonds. It is encoded directly by the gene's nucleotide sequence.
Primary vs. Higher-Order Structure
| Primary (1°) | Secondary (2°) | Tertiary (3°) | |
|---|---|---|---|
| What it describes | Amino acid sequence | Local folding patterns | Overall 3D shape |
| Bond type | Peptide bonds (covalent) | Hydrogen bonds | Multiple (H-bonds, disulfide, ionic, hydrophobic) |
| Examples | Met-Ala-Glu-Lys... | \(\alpha\)-helices, \(\beta\)-sheets | Globular fold |
| Determined by | Gene sequence | Backbone H-bonds | R-group interactions |
Breaking Peptide Bonds: Hydrolysis
Hydrolysis is the reverse of dehydration synthesis. Water is consumed to break the peptide bond, regenerating the free amino and carboxyl groups.
Naming Conventions: N to C
How to Analyze Primary Structure
Example 1: Counting Peptide Bonds
Problem: The hormone insulin consists of two polypeptide chains: the A chain (21 amino acids) and the B chain (30 amino acids). How many peptide bonds are in insulin?
Example 2: Estimating Molecular Weight
Problem: A polypeptide has 150 amino acids. Estimate its molecular weight, given that the average amino acid residue has a MW of ~110 Da (after water loss).
Example 3: Sickle Cell Disease
Problem: In sickle cell disease, the 6th amino acid of the \(\beta\)-globin chain changes from glutamic acid (Glu, charged) to valine (Val, nonpolar). Why does this single change cause red blood cells to sickle?
Common Mistakes
Summary of Key Concepts
| Concept | Details |
|---|---|
| Peptide Bond Formation | Dehydration synthesis: \(\text{-COOH} + \text{-NH}_2 \rightarrow \text{Peptide Bond} + \text{H}_2\text{O}\) |
| Peptide Bond Character | Partial double bond, trans configuration, ~\(1.33 \text{ \AA}\) |
| Primary Structure | Linear amino acid sequence, N-terminus to C-terminus |
| Bond Count | \(n\) residues = \(n - 1\) peptide bonds |
| MW Estimate | ~110 Da per residue (after water loss) |
| Hydrolysis | Water breaks peptide bond; catalyzed by proteases |
| Clinical Significance | Single residue change can alter function (sickle cell) |
Question 1 of 5
A polypeptide chain containing 200 amino acid residues has how many peptide bonds?
Question 2 of 5
Which property of the peptide bond is a direct consequence of resonance?
Question 3 of 5
In sickle cell disease, the substitution at position 6 of \(\beta\)-globin changes glutamic acid to valine. This primarily affects which level of protein structure?
Question 4 of 5
During peptide bond formation, which molecule is released as a byproduct?
Question 5 of 5
Which backbone dihedral angle is restricted due to the partial double-bond character of the peptide bond?