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 Multifunctional bacterial microswimmer able to deliver cargo and destroy itself
26.04.2018 | Max-Planck-Institut für Intelligente Systeme

nachricht ADP-ribosylation on the right track
26.04.2018 | Max-Planck-Institut für Biologie des Alterns

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Why we need erasable MRI scans

New technology could allow an MRI contrast agent to 'blink off,' helping doctors diagnose disease

Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

European particle-accelerator community publishes the first industry compendium

26.04.2018 | Physics and Astronomy

Multifunctional bacterial microswimmer able to deliver cargo and destroy itself

26.04.2018 | Life Sciences

Why we need erasable MRI scans

26.04.2018 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>