Peptides represent a billion-dollar market in the pharmaceutical industry, but they can generally only be taken as injections to avoid degradation by stomach enzymes. Scientists at EPFL have now developed a method to generate peptides that resist enzymatic degradation and can be taken orally.
Peptides are short chains of amino acids that occur in our body, in plants or bacteria to control diverse functions. Several peptides are used as drugs such as insulin, which controls the metabolism of sugar, and cyclosporine, which suppresses organ rejection after transplants. More than 40 peptides are already approved as drugs, generating revenues in the billions. There are several hundreds of peptide-based medications currently in clinical trials.
But almost none of these drug-peptides can be taken orally. Since peptides are an important part of food, the stomach and intestines harbor countless enzymes that can degrade them, meaning that most peptide-based medication do not survive the passage through the gastrointestinal tract.
Hope to generate more stable peptides came from “cyclic” peptides, whose ends are joined together by chemical bridges making them more stable than linear ones because their backbones are less flexible and thus harder to attack by enzymes. In 2018, the research group of Christian Heinis at EPFL developed a peptide format termed double-bridged peptides, where peptides are cyclized by two chemical bridges that provide even higher stability. Despite its success, most such peptides were not sufficiently stable to survive the enormous enzymatic pressure found in the gastrointestinal tract.
Now, Heinis’s group has developed a new method that identifies among billions of double-bridged peptides those that bind a disease target of interest and survive enzymes of the gastrointestinal tract. The method is published in Nature Biomedical Engineering, and involves three steps.
First, billions of genetically encoded random peptide sequences are cyclized by two chemical bridges that impose conformational constraints onto the peptides’ backbones so that they are more difficult to attack by enzymes.
Second, this library of peptides is exposed to enzymes from cow intestine to eliminate all those peptides that are not stable.
In the third and last step, the scientist dip target proteins into the pool of surviving peptides to fish out those that bind to the wanted disease target. “It’s a bit like searching a needle in a haystack, and this method makes this easy,” says Heinis.
With this method, the researchers have succeeded for the first time in evolving target-specific peptides that can resist breakdown in the gastrointestinal tract. For example, they gave mice a lead peptide that inhibits thrombin – an important anti-thrombosis target – in the form of a pill. The peptide remained intact in the stomach and intestines, and even though it reached the blood stream in rather small quantities, most of it remained fully intact across the entire gastrointestinal tract. This is a key step towards engineering oral peptide drugs.
Heinis’s group is now applying the new method to develop oral peptides that act directly on gastrointestinal targets, meaning that they don’t need to travel into the blood stream. “We are focusing on chronic inflammatory diseases of the gastrointestinal tract like Crohn’s disease and ulcerative colitis as well as bacterial infections,” says Heinis. “We have already succeeded in generating enzyme-resistant peptides against the interleukin-23 receptor, an important target of these diseases, which affect millions of patients worldwide without any oral drug available.”
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- Review Finds Erenumab Safe, Effective in Treating Chronic, Episodic Migraineon June 22, 2020 at 12:34 pm
In a review, researchers outlined the safety and efficacy of erenumab, the only monoclonal antibody built to interact with the calcitonin gene related peptide (CGRP) receptor rather than the CGRP ...
- ORMP: Positive Takeaways of Preliminary NASH Study Findingson June 20, 2020 at 5:13 pm
ORMP READ THE FULL ORMP RESEARCH REPORT Oramed Pharmaceuticals Inc. (NASDAQ:ORMP), a clinical-stage pharmaceutical company with a proprietary oral protein delivery platform technology, presented preli ...
- Phase-3 Clinical Trial of MT-7117 INITIATED IN THE U.S. for Rare DiseaseS, Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP)on June 19, 2020 at 10:46 am
this investigative oral treatment could provide another option for patients with EPP or XLP." MT-7117 is a novel synthetic, orally-administered, non-peptide small molecule, which acts as a selective ...
- Protagonist Therapeutics' PTG-300 Gets FDA's Orphan Drug Tagon June 18, 2020 at 8:14 am
Protagonist Therapeutics, Inc. PTGX announced that the FDA has granted an orphan drug designation to its injectable hepcidin mimetic PTG-300 for the treatment of polycythemia vera. The candidate is an ...
- Dompé Presents Phase II Clinical Trial Results for Ladarixin in New-Onset Type 1 Diabetes at the American Diabetes Association's Scientific Sessionson June 15, 2020 at 5:54 am
Dompé Farmaceutici S.p.A and Dompé U.S. Inc., (collectively Dompé) announced topline Phase 2 clinical trial (MEX0114) results for its investigational ...
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Altimmune Announces IND Clearance for a Phase 2 Trial of HepTcell™ Immunotherapeutic for the Treatment of Chronic Hepatitis Bon June 22, 2020 at 6:32 pm
Altimmune, Inc. (ALT), a clinical-stage biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to ...
- Hepcidin Mimetic PTG-300 Receives U.S. FDA Orphan Drug Designation for the Treatment of Polycythemia Veraon June 17, 2020 at 11:22 pm
"Receiving FDA orphan drug designation is another important ... technology platform to discover and develop novel peptide-based therapeutics to address significant unmet medical needs and ...
- Zealand Pharma strengthens executive team with new U.S. leadershipon June 14, 2020 at 11:35 pm
Copenhagen, June 15, 2020 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company changing lives with innovative peptide-based medicines, today announced the appointment of ...
- Computational approach to design peptide-based vaccine against SARS-Cov-2on June 10, 2020 at 11:31 pm
While several antiviral drugs have been tested, none has proved to be completely effective against the disease.
- Immunodominant epitopes identified for designing peptide-based vaccine against SARS-CoV-2on June 10, 2020 at 9:57 am
While several antiviral drugs have been tested, none has proved to be completely effective against the disease. In a study just published in the journal MDPI Vaccines, researchers from Bar-Ilan ...