Enzymes, DNA & Anticancer Drugs (AQA A Level Chemistry): Video

Hi, I'm Eleanor with 3 years of experience teaching Chemistry, and this video is about enzymes, DNA and anticancer drugs.

All three are about binding at a specific site. An enzyme's active site accepts only a substrate of matching shape, DNA's two strands hold together only through complementary base pairs, and a drug works by binding to one of those sites and stopping what normally happens there.

Enzymes are biological catalysts, and they are proteins with a specific three-dimensional shape. Part of that shape is the active site, and only a substrate whose shape matches it can bind. Drug action is also stereospecific and works the same way. Receptors are also proteins, and a drug binds to the receptor site and blocks it. DNA holds itself together by the same principle at a smaller scale, because each base will only hydrogen bond to one particular partner. And the anticancer drug, cisplatin, works by binding to DNA and stopping it replicating.

We'll start with enzymes and the active site, then drug receptors and why only one enantiomer works, then the structure of a DNA strand, then base pairing, and finish with how cisplatin works.

Enzymes are biological catalysts. They speed up chemical reactions in living organisms, and like any catalyst they are not used up in the process.

Enzymes are globular proteins, which means the polypeptide chain is folded into a specific three-dimensional shape. Within that shape is a region called the active site, and this is where the substrate, the molecule the enzyme acts on, binds to form an enzyme-substrate complex. The shape of the active site is what makes an enzyme specific: only a substrate with a complementary shape will fit, so each enzyme catalyses only its own reaction. That is the pattern the rest of this video keeps returning to.

Drugs act in a very similar way. Many drugs work by binding to a receptor site on a protein, and once the drug is bound it blocks the site so the molecule that would normally bind there cannot.

Because the binding depends on shape, the three-dimensional arrangement matters enormously. Where a drug molecule has a chiral centre, the two enantiomers are mirror images, and only one of them has the arrangement needed to fit the binding site. The other simply does not bind, so it has no therapeutic effect and may cause unwanted side effects. This is why pharmaceutical companies work to produce single-enantiomer drugs. Computers are used to model the shape of the drug and the receptor together, so that a molecule that fits can be designed rather than found by trial and error.

DNA is the molecule that carries genetic information, and it is built from a repeating unit made of three parts: a phosphate group, a sugar, and a nitrogenous base.

That three-part unit is called a nucleotide. The sugar is 2-deoxyribose, and the base can be one of four: adenine, thymine, guanine or cytosine. Nucleotides join together through their phosphate and sugar groups, and the result is a chain with a sugar-phosphate backbone running along it and the bases sticking out from the side. Two of these strands then run alongside one another in opposite directions, which is what antiparallel means.

What holds those two strands together is hydrogen bonding between the bases, and this is where the specific-site and specific shape idea appears again.

Each base will only pair with one particular partner. Adenine pairs with thymine, held by two hydrogen bonds. Guanine pairs with cytosine, held by three. The pairs are complementary, so the sequence on one strand fixes the sequence on the other. The two strands then twist around each other into the double helix. Just like the active site, this is a fit that only works one way round.

Cisplatin is an anticancer drug. It is a square planar complex of platinum with two chloride ligands and two ammonia ligands, in the cis arrangement.

Once it is inside the cell, the two chloride ligands are substituted by water ligands. The water ligands are then removed, which allows the platinum to form dative covalent bonds to nitrogen atoms on the guanine bases in DNA. That binding distorts the DNA structure and prevents it from replicating, so the cell cannot divide. Cancer cells divide rapidly, which is why the drug affects them, but it also affects other fast-growing cells in the body, and that is the source of its side effects.

An enzyme's active site accepts only a substrate whose shape matches it, and a drug receptor works the same way, which is why only one enantiomer of a chiral drug is active. In DNA, each base hydrogen bonds to only one partner: adenine with thymine, guanine with cytosine, holding the two antiparallel strands in a double helix. Cisplatin binds to two guanine bases and distorts the DNA so it cannot replicate. All three come back to the same idea: shape specific binding at a particular site.

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