Di-peptide synthesis simplified

Kyowa Hakko Kogyo has developed a new process for manufacturing amino acid dimers - also known as di-peptides - that could increase their use as components in infusions and enteral nutrition products.

Di-peptides consist of two amino acids connected with a peptide bond, and are generated naturally in the body as part of the process of protein breakdown. They are known to have properties and activities not seen with single amino acids.

The company said it intends to use the technology to develop a version of the amino acid glutamine that has good nutritional properties but is sparingly used in enteral nutrition products at present, but hope to broaden the use of di-peptides to a range of pharmaceutical and nutritional applications.

The amino acid is thought to have a protective effect for the enteric canal and gastric mucosa, with potential as an ulcer-treating agent, and cited as an important source of energy in the multiplication of immune cells and cells in wound-sites.

Kyowa said it intends to start commercial production by 2006 of alanyl-glutamine, a di-peptide composed of L-alanine and L-glutamine, based on its new production technology.

"Despite the nutritional effectiveness of L-glutamine, it has not been widely used in enteral nutrition products because of its poor stability and solubility in aqueous solutions," said Kyowa.

In contrast, alanyl-glutamine is stable against both heat and acid, is highly soluble, and functions as a source of L-glutamine in the body.

Kyowa Hakko's manufacturing process is based on a novel enzyme that directly connects amino acids together to create di-peptides without chemical modification. As this enzyme reacts with a variety of amino acids, it can also be applied to the manufacture of other di-peptides which may also have nutritional and pharmacological properties.

The Japanese company said it is actively seeking collaborations with other groups to explore the use of di-peptides in a range of healthcare applications.

Previously, chemical and/or enzymatic methods have been employed fordi-peptide synthesis. However, these methods have required the chemicalmodification of amino acids - potentially altering their activity - and can becontaminated with by-products. This creates problems in terms of quality, efficacy, yield, and environmental issues.

Kyowa Hakko anticipates the alanyl-glutamine market to be between 100 and 200 tons within a few years, and several hundred tons shortly thereafter.