Team:Imperial College London/M1 Detail

Polypeptides are classified according to their size and functional properties. Peptides are short chains of amino acids that often play a role in signalling and enzyme inhibition. At the other end of the spectrum, we have enzymes which are typically much larger with complex three dimensional structures. Enzymes serve to accelerate the rate at which chemical reactions occur in the cell.

To demonstrate The E.ncapsulator's versatility, we have chosen to showcase it with both enzymes and peptides. These two classes of polypeptide have very different properties that we have considered and catered for in The E.ncapsulator's design.

Peptide Delivery

While a few peptide drugs can be taken orally, many are suseptible to breakdown in the stomach making them suitable candidates for encapsulation. To achieve peptide compatibilty, The E.ncapsulator has been equiped with a special mechanism that facilaites peptide synthesis.

In all living cells, any polypeptide that is synthesised will ALWAYS begin with the same amino acid: methionine. However, polypeptides often undergo a series of processing steps before the final funtional form is reached. Functional peptides are commonly made by taking larger polypeptide precursors and chopping them up in a controlled manner. This process often results in functional peptides that do not have methionine as the first amino acid.

To enable The E.ncapsulator to produce peptides without inhibiting their functionality, we have developed a removable linker region that starts with the amino acid methionine. Following the release of the peptide in the intestine, a naturally occuring protease removes the linker region from the front of the peptide releasing the remainder in its functional form. The use of this linker region can be extended to any polypeptide that does not begin with methionine.

To showcase peptide delivery, we have chosen the pentapeptide (five amino acids)+++++++++. This represents the first iGEM entry to provide a treatment for pain, arousal and depression.

Enzyme Delivery

In the stomach, enzymes face two forms of assalt. The first is protease degradation and the second is denaturation. The high sensitivity of enzymes to these two forms of attack have made them challenging molecules to deliver to the intestine.

Enzymes = acid protection for 3d conformation

• Protein value = PAH = metabolic subcontraction from liver. Treatment for a genetic disease.

• Innovation = SDR for protease resistance

• Protein value = Cellulase = increase microbiome functionality