Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new synthetic amino acid for an emerging class of drugs

01.09.2014

One of the greatest challenges in modern medicine is developing drugs that are highly effective against a target, but with minimal toxicity and side-effects to the patient.

Such properties are directly related to the 3D structure of the drug molecule. Ideally, the drug should have a shape that is perfectly complementary to a disease-causing target, so that it binds it with high specificity. Publishing in Nature Chemistry, EPFL scientists have developed a synthetic amino acid that can impact the 3D structure of bioactive peptides and enhance their potency.

Peptides and proteins as drugs

Many of the drugs we use today are essentially naturally-occurring peptides (small) and proteins (large), both of which are made up with the amino acids found in all living organisms. Despite the enormous variety of peptides and proteins, there are only twenty natural amino acids, each with a different structure and chemical properties. When strung together in a sequence, amino acids create peptides and proteins with different 3D structures and, consequently, different biological functions.

... more about:
»EPFL »Ecole »Polytechnique »amino »cysteine »drugs »proteins »receptor

Until recently, the vast majority of amino acid-based drugs were the kinds occurring in nature: hormones such as insulin, antibiotics such as vancomycin, immunosuppressive drugs such as cyclosporine etc. But the mounting burden of diseases means that newer and more effective medications must be developed; for example, bacterial resistance is growing globally, pushing our need for novel antibiotics. One way to address this need is the cutting-edge field of directed evolution, which mimics natural selection in the lab to evolve and develop new peptides and proteins.

A new amino acid for new peptides

The team of Christian Heinis at EPFL has developed a synthetic amino acid whose unique structure can considerably increase the effectiveness of therapeutic peptides and proteins. The synthetic amino acid has a very similar structure to a natural amino acid called cysteine. Cysteine is unique among the twenty natural amino acids because it contains a sulfur group. This allows it to form a bridge with another cysteine, and thereby influence the overall 3D structure – and function – of a peptide or protein.

The EPFL researchers initially designed five cysteine-like amino acids, all with one crucial change: each one could form two bridges instead of just one. The team achieved this by replacing cysteine's single sulfur group with a branch containing two sulfur groups. After synthesizing the five new amino acids, the team integrated them into the structure of two bioactive peptides, one that inhibits an enzyme implicated in cancer, and one blocking a receptor found in neurons.

Testing only a handful of cyclic peptides with the synthetic amino acid, Heinis' team was able to identify several peptides that showed enhanced activities. The best inhibitor of the neuron receptor was 8-fold improved and the best protease inhibitor had even a 40-fold higher activity.

"This was unexpected", says Christian Heinis. "Usually when you tamper with a natural molecule, you end up making it worse. In this case, we found the exact opposite, which is very exciting."

The emerging class of bicyclic peptides

The team focuses on therapeutics, where they have a strong background in developing "bicyclic" peptides – peptides that contain two rings in their structure. Bicyclic peptides have grown into a new class of therapeutic peptides that can be used on disease target that conventional small molecules or large antibodies cannot reach. Heinis' group has generated bicyclic peptides against a range of disease targets using directed evolution. "In our work with bicyclic peptides, we learned that wide structural diversity in peptide libraries is key for achieving good binding. With this new amino acid, it is possible to produce highly diverse peptide structures."

Heinis aims now to use the new amino acid in directed evolution experiments. Its structural features and its ability to efficiently make cyclic peptides makes the synthetic amino acid a promising candidate for developing new, effective polycyclic peptides for targeted therapy.

###

Reference

Chen S. Gopalakrishnan R, Schaer T, Marger F, Hovius R, Bertrand D, Pojer F, Heinis C. Di-thiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. Nature Chemistry 31 August 2014. DOI: 10.1038/nchem.2043

Nik Papageorgiou | Eurek Alert!
Further information:
http://www.epfl.ch

Further reports about: EPFL Ecole Polytechnique amino cysteine drugs proteins receptor

More articles from Life Sciences:

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

nachricht How are pollen distributed in the air?
18.07.2019 | Leibniz-Institut für Troposphärenforschung e. V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

Im Focus: Modelling leads to the optimum size for platinum fuel cell catalysts: Activity of fuel cell catalysts doubled

An interdisciplinary research team at the Technical University of Munich (TUM) has built platinum nanoparticles for catalysis in fuel cells: The new size-optimized catalysts are twice as good as the best process commercially available today.

Fuel cells may well replace batteries as the power source for electric cars. They consume hydrogen, a gas which could be produced for example using surplus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Genetic differences between strains of Epstein-Barr virus can alter its activity

18.07.2019 | Health and Medicine

Algae-killing viruses spur nutrient recycling in oceans

18.07.2019 | Life Sciences

Machine learning platform guides pancreatic cyst management in patients

18.07.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>