Science News
from research organizations

Rapid chemical synthesis of proteins by a new amino acid partner

Date:
June 23, 2015
Source:
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University
Summary:
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 have succeeded in the first synthesis of oxazetidine amino acids as a new ligation partner for the rapid and chemoselective synthesis of proteins.
Share:
FULL STORY

Oxazetidine is a hydroxylamine in a four-membered ring form and exhibits high reactivity arising from its ring strain.
Credit: Copyright ITbM, Nagoya University

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.

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.


Story Source:

Materials provided by Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University. Note: Content may be edited for style and length.


Journal Reference:

  1. Ivano Pusterla, Jeffrey W. Bode. An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations. Nature Chemistry, 2015; DOI: 10.1038/nchem.2282

Cite This Page:

Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University. "Rapid chemical synthesis of proteins by a new amino acid partner." ScienceDaily. ScienceDaily, 23 June 2015. <www.sciencedaily.com/releases/2015/06/150623180447.htm>.
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University. (2015, June 23). Rapid chemical synthesis of proteins by a new amino acid partner. ScienceDaily. Retrieved May 24, 2017 from www.sciencedaily.com/releases/2015/06/150623180447.htm
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University. "Rapid chemical synthesis of proteins by a new amino acid partner." ScienceDaily. www.sciencedaily.com/releases/2015/06/150623180447.htm (accessed May 24, 2017).

RELATED STORIES