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 New Technique Maps Elusive Chemical Markers on Proteins
03.07.2015 | Salk Institute for Biological Studies

nachricht New approach to targeted cancer therapy
03.07.2015 | CECAD - Cluster of Excellence at the University of Cologne

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Viaducts with wind turbines, the new renewable energy source

Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.

The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Siemens receives order for offshore wind power plant in Great Britain

03.07.2015 | Press release

'Déjà vu all over again:' Research shows 'mulch fungus' causes turfgrass disease

03.07.2015 | Agricultural and Forestry Science

Discovery points to a new path toward a universal flu vaccine

03.07.2015 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>