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Polymers could help enzymes treat diseases

Posted on June 11, 2013
Schematic depiction of the behaviour of MX–polymer conjugates in the GI tract. After oral administration, MX–PG1 interacts with the negatively charged gastric mucin layer, which results in strong mucoadhesion. MX–PDL, MX–PAA and MX–mPEG do not (or only weakly) interact with the mucin layer. Credit: (c) Nature Chemistry (2013) doi:10.1038/nchem.1675

Schematic depiction of the behaviour of MX–polymer conjugates in the GI tract. After oral administration, MX–PG1 interacts with the negatively charged gastric mucin layer, which results in strong mucoadhesion. MX–PDL, MX–PAA and MX–mPEG do not (or only weakly) interact with the mucin layer. Credit: (c) Nature Chemistry (2013) doi:10.1038/nchem.1675

Conditions such as celiac disease, phenylketonuria, lactose intolerance and exocrine pancreatic disease involve abnormal enzyme activity. Enzymes administered orally could help sufferers. However, because enzymes, like all proteins, break down in the stomach and small intestine, they cannot usually survive in the gastrointestinal (GI) tract long enough to be effective. In a study published in Nature Chemistry, Jean-Christophe Leroux and his colleagues at the Swiss Federal Institute of Technology report they have found polymers that, when attached to enzymes, will prevent the enzymes from degrading in the GI tract. The research paves the way for new medical treatments.

Enzymes lose their structure and break up into their component parts easily. To correct this problem, biochemists have been attaching polymers to enzymes for decades. This makes the enzymes stable enough for use in pharmaceuticals. Doctors tend to administer these modified enzymes by injection or other non-oral routes, so they do not have to pass through the GI tract. Some oral medications contain enzymes; these have coatings to prevent stomach acid from attacking them. However, it is hard to predict how well the coatings will work in individual patients, so such medicines are not very reliable.

Recently, scientists modified an enzyme that breaks down phenylalanine, the amino acid that causes a problem for people with phenylketonuria (PKU), by combining it with the polymer polyethylene glycol (PEG). When given orally, this polymer-enzyme conjugate helped reduce phenylalanine levels in mice with PKU.

Leroux’s team, which had been studying celiac disease, tried to see if it could achieve similar results by attaching polymers to enzymes that break down gluten, the protein that triggers the disease. An enzyme that digests gluten before it reaches the small intestine would benefit celiac sufferers greatly.

Read more at: Phys.org

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