Researchers at the Swiss Federal Institute of Technology Lausanne (EPFL) have recently developed a novel method of testing and creating peptides that can survive degradation by stomach acids – these could potentially make up oral drugs for chronic inflammatory diseases of the gastrointestinal (GI) tract, unlike current medications that must be injected or administered in other ways.
Like proteins, peptides perform a huge array of functions in the body, but dissolve very quickly in the GI tract; stomach acids, in particular, will break down the bonds in proteins and peptides. So the EPFL researchers found a way to test strong, double-bridged peptides which could not only survive the stomach but also have useful effects.
For this, billions of random peptide sequences were combined with two chemical bridges to form double-bridged peptides and then exposed to enzymes from the digestive tracts of cows, to sort out those that survived. The “survivors” were later tested for any beneficial effect, based on their reaction(s) in a “peptide pool.”
The researchers managed to identify a new peptide in this manner: it inhibits thrombin, an enzyme that’s involved in blood clotting and so is targeted to treat thrombosis. In animal tests, the researchers gave the peptide orally to mice, and it remarkably survived in their stomachs and intestines.It suggests that these oral peptides might be best suited to targeting problems in that part of the body.
“We have already succeeded in generating enzyme-resistant peptides against the interleukin-23 receptor, an important target of diseases of the GI tract,” said Christian Heinis at EPFL. “Now, we are focusing on diseases like Crohn’s disease and ulcerative colitis as well as bacterial infections.”
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