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 Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>