Amino Acids and Peptide Bonds

Spec mapping — OCR H420 Module 2.1.2 — Biological molecules. This lesson covers the general structure of an amino acid (α-carbon + amine + carboxyl + R group), the diversity introduced by the 20 standard R groups, and the formation of peptide bonds by condensation. It establishes the chemistry that underpins protein structure (Lessons 9 and 10) (refer to the official OCR H420 specification document for exact wording).

Proteins are the most versatile and abundant class of biomolecules. They are polymers of amino acids joined by peptide bonds. Every protein in a living organism is synthesised from the same set of just 20 different amino acids, yet the variety of proteins produced is staggering — from structural keratin to catalytic enzymes, from oxygen-carrying haemoglobin to signalling hormones.

The structural elucidation of the first protein — bovine insulin — was achieved by Frederick Sanger in 1955, work that revealed each protein has a defined amino-acid sequence (its primary structure) and won Sanger his first Nobel Prize. The same technique applied to nucleic acids won Sanger his second Nobel (DNA sequencing) — making him one of only a handful of dual Nobel laureates. Sanger's work established that proteins are not random polymers but precise sequences that determine function.

1. The Structure of an Amino Acid

All 20 biologically encoded amino acids share the same general structure. Each amino acid has a central carbon (called the α-carbon) bonded to four different groups:

Amine group (–NH₂) — basic; accepts H⁺ to become –NH₃⁺
Carboxyl group (–COOH) — acidic; donates H⁺ to become –COO⁻
Hydrogen atom (–H)
R group (also called a side chain) — the only variable part

Key Definition — Amino acid: The monomer unit of proteins. Consists of a central α-carbon bonded to an amine group, a carboxyl group, a hydrogen atom, and a variable R group (side chain).

At physiological pH (pH ~7.4), the amine group is usually protonated (–NH₃⁺) and the carboxyl group is usually deprotonated (–COO⁻). The molecule exists as a zwitterion — a species with both positive and negative charges but a net charge of zero.

2. The R Group — Source of Diversity

All amino acids differ only in their R group. The R group determines:

Size, shape and flexibility
Polarity (hydrophobic vs hydrophilic)
Acidity or basicity
Ability to form hydrogen bonds, ionic bonds or disulfide bridges
Chemical reactivity in enzyme active sites

There are 20 standard R groups encoded by the genetic code, often classified into:

Category	Examples	Key feature
Non-polar (hydrophobic)	Glycine, alanine, valine, leucine, isoleucine	Hydrocarbon chains; buried inside proteins
Polar uncharged	Serine, threonine, asparagine, glutamine	–OH or –NH₂ groups; form hydrogen bonds
Acidic (negatively charged)	Aspartate, glutamate	–COOH side chain; ionic interactions
Basic (positively charged)	Lysine, arginine, histidine	–NH₂ or imidazole; ionic interactions
Containing sulfur	Cysteine, methionine	Cysteine can form disulfide bridges
Aromatic	Phenylalanine, tyrosine, tryptophan	Ring structures; hydrophobic
Imino acid	Proline	R group loops back to amine; restricts flexibility

Exam Tip: You are not required to memorise all 20 structures at A-Level, but you should know that cysteine forms disulfide bridges, glycine has just –H as its R group (the smallest), and proline introduces kinks in the chain.

3. The Peptide Bond

When two amino acids join, the carboxyl group of one amino acid reacts with the amine group of another in a condensation reaction. A water molecule is released, and a new covalent bond is formed between the carbon (of the original –COOH) and the nitrogen (of the original –NH₂). This bond is the peptide bond.

Key Definition — Peptide bond: The covalent bond (–CO–NH–) formed between the carboxyl group of one amino acid and the amine group of another, with the release of a water molecule in a condensation reaction.

The product is a dipeptide (two amino acids joined). Further condensation reactions build longer chains:

Dipeptide — 2 amino acids
Tripeptide — 3 amino acids
Oligopeptide — a few (usually 3–20) amino acids
Polypeptide — many (typically more than 20) amino acids
Protein — one or more polypeptides folded into a functional three-dimensional structure

For n amino acids joined, there are (n − 1) peptide bonds and (n − 1) water molecules released.

4. Hydrolysis of Peptide Bonds

The reverse reaction — adding a water molecule to break a peptide bond — is hydrolysis. In organisms, this is catalysed by proteases (also called peptidases). Examples:

Pepsin — in the stomach; hydrolyses peptide bonds adjacent to aromatic amino acids.
Trypsin and chymotrypsin — in the small intestine.
Exopeptidases — cleave terminal amino acids from the ends of chains.
Endopeptidases — cleave internal peptide bonds.

Protein digestion involves sequential action of multiple proteases, breaking polypeptides down into individual amino acids that can be absorbed across the intestinal epithelium by co-transport with Na⁺.

5. The Peptide Group — a Planar, Rigid Unit

Although peptide bonds are drawn as single bonds, they have partial double-bond character due to resonance between the carbonyl carbon and the nitrogen lone pair. Consequences:

The peptide group (–CO–NH–) is planar and essentially rigid.
Rotation around the C–N bond is restricted.
The adjacent single bonds (to the α-carbons) can rotate freely, giving the chain flexibility only at the α-carbons.
This restricted geometry is crucial for the formation of secondary structures (α-helix, β-pleated sheet).

6. Directionality of a Polypeptide

A polypeptide chain has two distinct ends:

N-terminus — the end with a free amine group (written on the left by convention).
C-terminus — the end with a free carboxyl group (written on the right by convention).

Polypeptides are synthesised on ribosomes from the N-terminus to the C-terminus, and their sequences are written in the same direction.

7. Drawing a Dipeptide: Worked Example

Draw the dipeptide formed from glycine (R = H) and alanine (R = CH₃).

Step 1: Write both amino acids with –COOH on the right and –NH₂ on the left:

Amino acid	Structure
Glycine	H₂N — CH(H) — COOH
Alanine	H₂N — CH(CH₃) — COOH

Step 2: Remove –OH from glycine's –COOH and –H from alanine's –NH₂ (together forming H₂O).

Step 3: Draw the new C–N peptide bond:

Dipeptide product: H₂N — CH(H) — CO — NH — CH(CH₃) — COOH + H₂O.

The middle –CO–NH– linkage is the peptide bond; the left residue is glycine, the right is alanine.

The peptide bond is the –CO–NH– in the middle.

8. Number of Possible Polypeptides

With 20 different amino acids, the number of possible polypeptides of length n is 20ⁿ. For a modest protein of 100 amino acids, this gives 20¹⁰⁰ ≈ 10¹³⁰ possible sequences — more than the number of atoms in the observable universe. This astronomical number explains the extraordinary diversity of protein function.

Exam Tips

Always label all four groups on the α-carbon when drawing an amino acid: –NH₂, –COOH, –H and –R.
State that the peptide bond is –CO–NH– and that it forms by condensation with loss of water.
Mention that proteases catalyse the hydrolysis of peptide bonds.
Know that R groups determine protein folding and function.

Common Exam Mistakes

Drawing the amine group as –NH instead of –NH₂.
Forgetting the –H on the α-carbon.
Writing "proteins are made of amino acids and peptide bonds" — amino acids are joined by peptide bonds.
Saying "all amino acids are the same" — they differ in their R group.
Writing "peptide bond forms between –NH and –COO" instead of between amine and carboxyl groups.
Confusing condensation (water released) with hydrolysis (water added).

9. R Group Examples — Five Representative Side Chains

Amino acid	R group	Property	Functional role
Glycine (Gly, G)	–H	Smallest; very flexible	Fits in tight turns of helix/sheet; abundant in collagen triple helix
Cysteine (Cys, C)	–CH₂–SH	Sulfhydryl (thiol)	Forms disulfide bridges (–S–S–) between Cys residues; stabilises tertiary structure
Lysine (Lys, K)	–(CH₂)₄–NH₃⁺	Basic, positively charged	Ionic interactions with acidic R groups (Asp, Glu); active in histone-DNA binding
Glutamate (Glu, E)	–(CH₂)₂–COO⁻	Acidic, negatively charged	Ionic interactions with basic R groups; catalytic role in many enzyme active sites
Phenylalanine (Phe, F)	–CH₂–C₆H₅	Aromatic, hydrophobic	Hydrophobic core packing; π-stacking interactions in DNA-binding proteins

These five examples illustrate the chemical range covered by the 20 standard amino acids — from non-reactive (Gly) through redox-active (Cys), through cations and anions (Lys, Glu) to aromatic π-systems (Phe). The diversity is what makes proteins biochemically versatile.

10. Synoptic Links

This lesson connects across the OCR H420 specification:

Lesson 8: Amino Acids and Peptide Bonds