SL MD5 Targeting bacteria

Penicillin first became available in the second world war – it saved many lives. It is an enzyme inhibitor and stops the construction of cell walls. Bacteria die as a result.

Fleming was growing bacteria Fleming was growing bacteria. On return from a holiday, he noticed that one petri dish had been accidentally contaminated with a mould. No bacterial colonies seemed to be growing in the vicinity of the mould. He called the chemicals given off by penicillium notatum penicillins. At first, penicillin was only used as an antiseptic for local use. A decade later, it was found effective in treating streptococcal infections in mice and later used on humans. In the 1940s, penicillin was made in bulk and heralded as a wonder drug. 1928

The mould makes several antibiotic compounds The mould makes several antibiotic compounds. These were isolated and called penicillin F, G, K and X etc. It was found that the mould could be encouraged to produce just one compound by altering the nutrient which it was grown on. So, using phenylethanoic acid in the agar yielded just penicillin G.

Penicillin G is only effective against a limited variety of bacteria Penicillin G is only effective against a limited variety of bacteria. Also, it has to be injected because acidity in the stomach affects it’s activity. Penicillin V can be taken orally.

6-APA 1950s 6-aminopenicillanic acid The National Health Service was set up in 1948. Beechams were looking more closely at the preparation of antibiotics. They found and isolated the penicillin core. 6-aminopenicillanic acid 1950s

It was now possible to make a semi-synthetic penicillin It was now possible to make a semi-synthetic penicillin. The 6-APA could be obtained from hydrolysis of a peptide link in penicillin G then a side chain attached. What type of reaction is this?

Β-lactam ring H2N – CH2 – CH2- COOH All the penicillins have a beta lactam ring. Imagine it being made from the beta amino acid. The rings open easily and they react readily with acids and alkalis. This accounted for the difficulties in isolating and purifying the first penicillins. Β-lactam ring H2N – CH2 – CH2- COOH

Try Ass 11.

Polypeptide cross links – enzyme needed for formation Bacteria are protected by a rigid cell wall. Polysaccharide chains are linked by polypeptide cross links. Penicillin reacts with the enzyme necessary for the formation of the polypeptides. The cell wall is weakened, eventually the contents of the bacteria cells burst out and it dies. Polypeptide cross links – enzyme needed for formation

The cell wall in a bacterium is different to that of plants and to the cell membrane in animals. In bacteria, D – alanine is one of the amino acids used in the cross link. In plants and animals, the L- isomer is present. Penicillins target bacterium cells only.

Sometimes, penicillin resistant bacteria emerge Sometimes, penicillin resistant bacteria emerge. These bacteria produce an enzyme called β-lactamase which attacks the β-lactam ring in penicillins and makes them ineffective. Chemists have had success in making new side chains. It was also found that mixing clavulanic acid with previously ineffective antibiotics works. This inhibits the action of the β-lactamase enzyme.