Key Terminology
Term Definition
Amino Acid Organic molecule that is made up of a basic amino group (−NH2), an acidic
carboxyl group (−COOH), and an R group specific to each amino acid
Zwitterion A molecule or ion having separate positively and negatively charged groups
Protein Organic compounds composed of chains of amino acids and are an essential part
of all living organisms
Primary Protein
Structure
Sequence of amino acids in a polypeptide chain
Secondary Protein
Structure
Interactions between amino acids in chains cause the chains to twist into either
α-helices or β-pleated sheets
Tertiary Protein
Structure
The final three-dimensional shape of a protein chain, with chemical bonds and
hydrophobic interactions maintaining this structure
Globular Protein Spherical shape caused by highly folded polypeptide chain with a tertiary
structure, with hydrophilic groups on the inside
Enzyme Globular proteins, which acts as biological catalysts
DNA The main constituent of chromosomes; the carrier of the genetic code
Cisplatin A cytotoxic drug used in cancer chemotherapy
Amino Acids and Protein Structure
Amino acids are the building blocks of proteins, and have two fictional groups – NH2 and COOH. There
are 20 naturally occurring amino acids which are all α amino acids. Since the COOH has a tendency to
lose a proton, and the amine group has a tendency to accept a proton, amino acids exist as zwitterions,
with a permanent positive and negative charge. This ionic behaviour
means amino acids have high melting points and are very soluble.
In strongly acidic conditions, NH2 accepts a proton to form a cation. In
strongly alkaline conditions, the -OH group loses a H+
to form an anion
Proteins are sequences of amino acids joined by peptide links.
Hydrolysis of proteins gives the constituent amino acids. The sequence of amino acids in a polypeptide
chain is known as the primary structure of a protein.
Interactions between the residual groups cause the chain to twist and fold into its secondary structure,
either an α-helix or β-pleated sheet.
• In an α-helix, hydrogen bonds form between the C=O of the carboxylic acid group and the -NH
of the amine group, stabilising this shape.
• In β-pleated sheets, several chains may link together, with hydrogen bonds
holding the parallel chains in this arrangement
In the tertiary structure, the protein chain folds to produce a precise 3D shape. Interactions such as
hydrogen bonding, ionic bonds and van der Waals cause the protein to hold this shape. Disulfide bridges
are also important; these are covalent bonds between cysteine R groups, containing -SH.
To determine structure, the first step is to determine the primary structure. First, the protein is refluxed
for 24 hours with 6M HCl, causing hydrolysis into constituent amino acids, which can then be separated
by TLC. The distance each amino acid travels depends on its affinity for the solvent compared to that
for the stationary phase. Once movement is complete, remove from the tank and spray with the
developing agent ninhydrin, or view under UV light to identify the spots. Calculate the Rf to identify the
amino acids. 2D TLC may be needed as multiple amino acids may have the same Rf
Enzymes
Enzymes are globular proteins, which acts as biological catalysts. Enzymes are extremely specific and
are optimised for a single substrate due to the highly precise shape of the active site. The active site is
so specific that enzymes only catalyse reactions of one enantiomer from a pair – hence they are
stereospecific. This is also because the amino acids except glycine are chiral.
Whilst a substrate is bonded to the enzyme temporarily, intermolecular forces promote the movement
of electrons within the substance that lowers the activation energy for the reaction.
Enzymes control almost all reactions in organisms, and drugs can be designed to affect their action. A
drug can act as an enzyme inhibitor by blocking the active site by competitive inhibition, excluding the
substrate. Computers can be used to help design such drugs by modelling.
DNA
DNA stands for deoxyribonucleic acid, and is the carrier of the genetic code. A
nucleotide is made up from a phosphate ion bonded to 2-deoxyribose which is in turn
bonded to one of the four nitrogenous bases adenine, cytosine, guanine and thymine.
A single strand of DNA is a polymer of nucleotides linked by covalent bonds between
the phosphate group of one nucleotide and the 2-deoxyribose of another. This results
in a sugar-phosphate polymer chain with bases attached to the sugars in the chain. DNA is therefore a
condensation polymer.
DNA exists as two complementary strands twisted into a double helix.
The structures of the bases are given in the data booklet. A forms a double hydrogen bond with T, and
C forms a triple bond with G. These are the complementary base pairings.
DNA must replicate before cell division. The hydrogen bonds between the strands break and new
nucleotides move in and pair with the exposed bases in strands, producing two new identical helices
after polymerisation.
Cisplatin – Anticancer Drug
Cancer is a disease where cell division is uncontrolled. The Pt(II) complex
cisplatin is used as an anticancer drug. Cisplatin prevents DNA replication
in cancer cells by a ligand replacement reaction with DNA in which a bond
is formed between platinum and the nitrogen atom on two adjacent
guanine bases. This happens as the N atoms on the guanine have lone
electron pairs which form dative covalent bonds with the platinum,
displacing the chloride ions as they are better ligands. This distorts the
shape of the helix and prevents replication.
Cisplatin has side effects, as it binds to DNA in healthy cells as well, although it has less of an effect here
as rate of cell division is far lower. However, healthy cells with a rapid division rate e.g. hair cells are
significantly affected. Research attempts to assess the balance between the benefits and the adverse
effects of drugs.
