Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rapid chemical synthesis of proteins by a new amino acid partner

29.06.2015

The development of new methods for the chemical synthesis of proteins is highly significant to access a range of proteins inaccessible by conventional approaches. Chemists at ETH-Zürich and ITbM have succeeded in the first synthesis of oxazetidine amino acids as a new ligation partner for the rapid and chemoselective synthesis of proteins.

The development of new methods for the chemical synthesis of proteins is highly significant to access a range of proteins inaccessible by conventional approaches. Dr. Ivano Pusterla and Prof. Jeffery Bode of ETH-Zürich and Nagoya University's Institute of Transformative Bio-Molecules (ITbM) have succeeded in the first synthesis of oxazetidine amino acids as a new ligation partner for the rapid and chemoselective synthesis of proteins.


Copyright : ITbM, Nagoya University

Oxazetidine is a hydroxylamine in a four-membered ring form and exhibits high reactivity arising from its ring strain. The KAHA ligation reaction developed by Bode’s group has been used to synthesize various proteins by the reaction between α-ketoacids and oxaprolines, a five-membered hydroxylamine ring. One limitation of this previous reaction system was that a non-native homoserine residue is introduced in the ligation site.

In this study, Bode has showed that oxazetidine-containing peptides react with α-ketoacids to undergo KAHA ligation at lower concentrations and at milder temperatures to produce proteins that contain native serine residues. The oxazetidine amino acid is formally an oxidized form of serine, which has a relatively high abundance and can replace other amino acid residues without affecting the overall folding or function of proteins.

This reaction system was applied towards the synthesis of a 100-residue calcium-binding protein, S100A4, which is usually difficult to access by native chemical ligation or other amide-forming reactions. The high reaction rate, chemoselectivity and versatility of this new native amide-forming ligation reaction using oxazetidine amino acids is envisaged to become a powerful method for the rapid chemical synthesis of useful proteins.

This article "An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations" by Ivano Pusterla & Jeffrey W. Bode is published online on June 23, 2015 in Nature Chemistry as an Advanced Online Publication.
DOI: 10.1038/nchem.2282 ( http://dx.doi.org/10.1038/nchem.2282 )

About WPI-ITbM ( http://www.itbm.nagoya-u.ac.jp/ )
The World Premier International Research Center Initiative (WPI) for the Institute of Transformative Bio-Molecules (ITbM) at Nagoya University in Japan is committed to advance the integration of synthetic chemistry, plant/animal biology and theoretical science, all of which are traditionally strong fields in the university. As part of the Japanese science ministry’s MEXT program, ITbM aims to develop transformative bio-molecules, innovative functional molecules capable of bringing about fundamental change to biological science and technology. Research at ITbM is carried out in a “Mix-Lab” style, where international young researchers from multidisciplinary fields work together side-by-side in the same lab. Through these endeavors, ITbM will create “transformative bio-molecules” that will dramatically change the way of research in chemistry, biology and other related fields to solve urgent problems, such as environmental issues, food production and medical technology that have a significant impact on the society.

Author Contact
Professor Jeffrey Bode
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University
Furo-Cho, Chikusa-ku, Nagoya 464-8601, Japan
E-mail: bode@itbm.nagoya-u.ac.jp

ETH-Zürich
Laboratory of Organic Chemistry
HCI F 315, Wolfgang-Pauli-Strasse 10
8093 Zürich, Switzerland
Tel: +41-44-633-2103
E-mail: bode@org.chem.ethz.ch

Public Relations Contact
Dr. Ayako Miyazaki
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University
Furo-Cho, Chikusa-ku, Nagoya 464-8601, Japan
TEL: +81-52-789-4999 FAX: +81-52-789-3240
E-mail: press@itbm.nagoya-u.ac.jp

Nagoya University Public Relations Office
TEL: +81-52-789-2016 FAX: +81-52-788-6272
E-mail: kouho@adm.nagoya-u.ac.jp

Associated links
ITbM Nagoya University article

Journal information

Nature Chemistry

Ayako Miyazaki | ResearchSEA
Further information:
http://www.researchsea.com

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

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 evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

NSF-supported researchers to present new results on hurricanes and other extreme events

19.07.2018 | Earth Sciences

Scientists uncover the role of a protein in production & survival of myelin-forming cells

19.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>