Engineering Proteins

EP1 Christopher’s Story

Proteins

• Greek prōteios ‘primary’ > German Protein > French protéine
• Primary biological molecule
• Many molecules in living things are proteins
• Proteins are natural polymers
• Proteins have molecular masses up to 100,000
• Proteins form muscle, cell membranes, hair, nails and feathers
• All enzymes are proteins. They are biological catalysts
• Many hormones are proteins, although not all are
• Many binding substances are proteins, for example haemoglobin

Insulin history

• Insulin is a hormone and a protein, which controls the uptake of glucose and some other sugars by our cells
• Isolated in 1921 in Toronto by young scientists F G Banting and C H Best
• Available for diabetes treatment in 1922, from pig or cow pancreas
• Diabetes was previously fatal, a miserable disease to have
• Biotechnology provides modern insulin although it doesn’t mimic insulin in non-diabetics exactly

Insulin in the body

• There is a low background blood insulin concentration
• Insulin is released rapidly after eating
• Insulin concentration peaks soon after eating then falls off
• It’s stored in special pancreatic cells in hexamer form, due to surface interactions
• A rise in blood glucose concentration triggers insulin release
• As blood dilutes the insulin concentration (from 10^-3 to 10^-6 mol dm^-3) the hexamers break down into dimers and at even lower concentration (10^-8 mol dm^-3), monomers
• These monomers fit through capillary membranes
• Insulin monomers are quickly transported to where they are needed
• Protein engineering aimed to produce stable monameric insulin in the eighties

Amino acids

Amino acids consist of an amino group (-NH₂) and a carboxylic acid group (-COOH). The central carbon atom is called the α-carbon, giving these amino acids the name α-amino acids. The α-carbon is the one adjacent to a functional group. The R group differs in different amino acids.