Chemistry (9620) | Amino acids and proteins

Amino Acids and Proteins: The Molecules of Life (International A2)

Welcome to one of the most fascinating topics in Organic Chemistry! This chapter focuses on amino acids and proteins—the fundamental molecules that make up living organisms, from your hair to your enzymes. Understanding their structure and bonding is key to grasping how life works and how we can design modern drugs.

Don't worry if these long names seem daunting. We will break down the structures piece by piece. Once you understand the basic building block (the amino acid), everything else snaps into place!

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1. Amino Acids: The Building Blocks

Amino acids are special organic molecules because they contain two different functional groups that give them unique properties:

• An amino group ($\text{NH}_2$): This is a basic group because the nitrogen atom has a lone pair of electrons, allowing it to act as a proton acceptor.
• A carboxylic acid group ($\text{COOH}$): This is an acidic group, able to donate a proton.

They also have a central carbon atom (the $\alpha$-carbon) and a variable side chain called the R-group. It is the R-group that makes each of the 20 common amino acids unique.

1.1 Amphoteric Nature and Zwitterions

Because amino acids contain both an acidic ($\text{COOH}$) group and a basic ($\text{NH}_2$) group, they are amphoteric (meaning they can act as both an acid and a base).

The Zwitterion Structure

In a neutral solution (like pure water), the carboxylic acid group reacts internally with the amino group. The acid group ($\text{COOH}$) loses a proton ($\text{H}^+$) and the base group ($\text{NH}_2$) gains it. This forms a species called a zwitterion.

• The $\text{COOH}$ becomes $\text{COO}^-$ (a negative ion).
• The $\text{NH}_2$ becomes $\text{NH}_3^+$ (a positive ion).

A zwitterion is a molecule that carries both a positive and a negative charge, but has a net overall charge of zero.

Analogy: Think of a zwitterion like a rechargeable battery that is fully charged but not plugged in—it holds both positive and negative terminals, making it electrically neutral overall.

1.2 Ionic Forms in Acidic and Alkaline Solutions

The structure of the amino acid changes depending on the pH of the solution:

1. In Acid Solution (High $\text{H}^+$ concentration)

If we add acid, there is an excess of $\text{H}^+$ ions. The $\text{COO}^-$ group on the zwitterion accepts a proton, returning it to the neutral $\text{COOH}$ group. The overall ion is positively charged.

$$ \text{Zwitterion} + \text{H}^+ \rightarrow \text{Positive Ion} \quad (\text{H}_3\text{N}^+-\text{CHR}-\text{COOH}) $$

2. In Alkaline Solution (High $\text{OH}^-$ concentration)

If we add alkali, there is a shortage of $\text{H}^+$ ions. The $\text{NH}_3^+$ group on the zwitterion loses a proton to the strong base ($\text{OH}^-$), returning it to the neutral $\text{NH}_2$ group. The overall ion is negatively charged.

$$ \text{Zwitterion} + \text{OH}^- \rightarrow \text{Negative Ion} + \text{H}_2\text{O} \quad (\text{H}_2\text{N}-\text{CHR}-\text{COO}^-) $$

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2. Proteins and Peptides

Proteins are biological macromolecules formed when many amino acids link together. Small chains are called peptides; large chains are called proteins.

2.1 The Peptide Link (Condensation Polymerisation)

Amino acids join together through a condensation reaction, releasing a molecule of water ($\text{H}_2\text{O}$).

The reaction occurs between:

• The $\text{COOH}$ group of one amino acid, and
• The $\text{NH}_2$ group of another amino acid.

The resulting covalent bond ($\text{-CO-NH-}$ ) is called a peptide link or amide link.

$$ \text{H}_2\text{N}-\text{R}_1-\text{COOH} + \text{H}_2\text{N}-\text{R}_2-\text{COOH} \rightarrow \text{H}_2\text{N}-\text{R}_1-\text{CO}-\text{NH}-\text{R}_2-\text{COOH} + \text{H}_2\text{O} $$

A chain formed from two amino acids is a dipeptide. A chain formed from many amino acids is a polypeptide (protein).

2.2 Drawing Peptides

You must be able to draw the structure of a peptide formed from up to three amino acids.

Step-by-Step for a Dipeptide:

1. Draw the first amino acid ($\text{H}_2\text{N}-\text{CHR}_1-\text{COOH}$).
2. Draw the second amino acid ($\text{H}_2\text{N}-\text{CHR}_2-\text{COOH}$) beside it.
3. Remove $\text{H}_2\text{O}$ (an $\text{OH}$ from the $\text{COOH}$ and an $\text{H}$ from the $\text{NH}_2$).
4. Draw the resulting $\text{-CO-NH-}$ peptide link between the two residues.

2.3 Hydrolysis of Peptides

The reverse of condensation is hydrolysis (breaking the bond using water).

• Peptide links are broken down when the peptide is heated with dilute acid or dilute alkali (or naturally, by enzymes).
• Hydrolysis breaks the peptide link ($\text{-CO-NH-}$ ) and regenerates the constituent amino acids.
• If acid is used for hydrolysis, the amino acids will be released in their acidic ion forms ($\text{NH}_3^+$/$\text{COOH}$).

You should be able to draw the structures of the amino acids formed after hydrolysis of a given peptide.

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3. Levels of Protein Structure

The final function of a protein depends entirely on its specific 3D shape, which is categorised into three main levels.

3.1 Primary Structure

The primary structure is simply the sequence of amino acids linked together by peptide bonds.

Key Takeaway: The primary structure dictates all other levels of structure. Get the sequence wrong, and the entire 3D shape—and thus the function—will be wrong.

3.2 Secondary Structure

The secondary structure refers to the local folding of the polypeptide chain into repeating, regular shapes. These structures are maintained by hydrogen bonding between the $\text{C=O}$ group of one peptide link and the $\text{N-H}$ group of another further down the chain.

• $\alpha$-Helix: A spiral or coiled structure. Hydrogen bonds run parallel to the coil axis.
• $\beta$-Pleated Sheet: A folded, zigzag structure. Hydrogen bonds form between chains lying side-by-side.

3.3 Tertiary Structure

The tertiary structure is the complex, overall three-dimensional shape of a single polypeptide chain. This is maintained by interactions between the R-groups (side chains) of the amino acids.

The bonds responsible for the tertiary structure are:

1. Sulfur-Sulfur Bonds (Disulfide Bridges): These are strong covalent bonds formed between the sulfur atoms of two cysteine amino acids. These are critical for structural stability.
2. Hydrogen bonds: Weak bonds between polar R-groups (e.g., $\text{OH}$ and $\text{NH}$).
3. Ionic bonds: Electrostatic attractions between $\text{NH}_3^+$ and $\text{COO}^-$ groups on charged R-groups.
4. van der Waals forces: Very weak forces between non-polar R-groups.

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4. Analysis of Amino Acids: Chromatography

To identify the amino acids present in a protein, the protein must first be hydrolysed. The resulting mixture of amino acids can then be separated using thin-layer chromatography (TLC).

4.1 Thin-Layer Chromatography (TLC)

TLC separates compounds based on their differential solubility in the mobile phase (solvent) and their adsorption onto the stationary phase (the plate).

The Process:

1. Amino acid mixture is spotted onto the TLC plate (stationary phase).
2. The plate is placed in a solvent (mobile phase).
3. The solvent moves up the plate, carrying the amino acids with it.
4. Amino acids that are highly soluble in the solvent or weakly adsorbed to the plate travel further.

4.2 Locating and Identifying Amino Acids

Amino acids are often colourless, so a developing agent is needed to locate them on the plate:

• Ninhydrin: A chemical spray that reacts with amino acids to produce purple-coloured spots.
• UV Light: If the amino acid R-group fluoresces, it can be detected under UV light.

4.3 The $R_f$ Value

To identify an unknown amino acid, we calculate its retardation factor, $R_f$. This value is compared to standard $R_f$ values measured under the same conditions (same solvent, same temperature).

$$ R_f = \frac{\text{Distance travelled by spot}}{\text{Distance travelled by solvent front}} $$

You must be able to calculate the $R_f$ value from a chromatogram.

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5. Action of Anticancer Drugs: Cisplatin

The Platinum(II) complex cisplatin ($\text{Pt}(\text{NH}_3)_2\text{Cl}_2$) is an important drug used in chemotherapy to treat various cancers.

5.1 How Cisplatin Works

Cisplatin works by preventing cancer cells from replicating their DNA:

1. Cisplatin enters the cell.
2. It undergoes a ligand replacement reaction (a substitution reaction) where the chloride ligands ($\text{Cl}^-$) are replaced by water molecules.
3. This reactive platinum complex then targets the DNA molecule.
4. The platinum ion forms a strong coordinate bond with the nitrogen atoms found on the guanine bases of the DNA strands.
5. The complex forms cross-links or kinks in the DNA structure, meaning the DNA cannot be unwound properly for replication or transcription.
6. Since the cancer cell cannot replicate or divide, it dies.

5.2 Benefits vs. Adverse Effects

The development of drugs like cisplatin forces society to assess the balance between life-saving benefits and serious risks.

• Benefit: Effective treatment against several highly aggressive cancers.
• Adverse Effects: The drug often affects fast-dividing non-cancerous cells (like hair follicle cells, bone marrow cells, and gut lining cells), leading to severe side effects such as nausea, hair loss, and immune suppression.

Don't forget: In your exam, you need to explain why cisplatin prevents DNA replication (by bonding to DNA bases) and explain the adverse effects (due to non-specific targeting of rapidly dividing healthy cells).

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You've mastered the chemical structure of life's essential molecules! Keep practicing those structures—especially the zwitterion and peptide link—and you'll ace this topic!