Protein applications Flashcards
Why are therapeutics proteins used rather than small molecules?
Many small molecules are inhibitors of proteins.
But proteins have complex functions that cannot be performed by small molecules.
Proteins form specific interactions, and can replace enzyme activities.
Proteins can block protein-protein interactions, and this is difficult for small molecules.
What are the functions of proteins with enzymatic activity?
Replace a deficient protein.
Augment an existing pathway.
Provide a novel activity.
Where are proteins sourced from?
May be purified from natural sources or recombinant - unlimited supply, safe.
Can be wild type or modified to enhance properties.
What is insulin?
Small protein - 51 amino acids.
Produced by pancreatic B-cells.
Stimulates glycogenesis and inhibits glucose production.
What is type 1 diabetes?
B cells are destroyed and insulin is not produced.
Causes high blood sugar levels.
What is pancreatic insufficiency?
Caused by:
Pancreatitis - if pancreas is removed, can’t release digestive enzymes into small intestine.
Pancreatectomy
Cystic fibrosis.
What is the treatment for pancreatic insufficiency?
Extract of digestive enzymes - chymotrypsin, amylase, lipase - is made into enteric-coated capsules - Pancrelipase.
This goes through stomach without being digested, then released in stomach.
What is a1 antitrypsin?
Protein synthesised by liver.
Inhibits neutrophil elastase.
Mutations cause misfolding and prevent secretion, so there is too much neutrophil elastase, causes liver damage and lung damage - COPD.
What is a1-antitrypsin deficiency treatment?
Intravenous infusin of a1 antitrypsin, cannot be orally taken as would be digested.
Does not reverse the damage of the disease, but prevents progression.
What is the theme of therapeutic proteins?
Break down unwanted things in the body.
E.g. asparaginase breaks down asparagine to aspartate, so leukemia cells can’t proliferate.
What are the benefits of recombinant therapeutic proteins?
Safer, limitless supply, can be modified:
Point mutations can be introduced to alter activity and stability.
Alter glycosylation to alter stability.
Pegylation to increase half-life - bigger and more soluble.
What are chimeric proteins?
Can alter proteins so that they perform the functions of other proteins, within one protein.
What is Herceptin?
Humanised anti-Her2 antibody.
HER2 oncoprotein is overexpressed in many cancers.
It is a Receptor tyrosine kinase, activated by dimerisation, drives cancer proliferation.
What are antibody drug conjugates (ADCs)?
Attach antibody to toxic cargo - binds to cell surface proteins on diseased cells, delivers toxin to cells, so cell dies.
What are immune checkpoint inhibitors?
Cancer cell presents antigenic peptides to T cell.
T cell recognises antigen and destroys the cancer cell.
But molecules interact with T cell and prevent it from killing cancer.
By inhibiting these molecules, can destroy the tumour cells.
