Peptide synthesis made simple with new enzyme

Peptides are widely used in creating medicines and the total market size for peptide-based drugs is already estimated at around $10 billion. There are currently many types of manufacturing processes, but these are often lengthy and complex and there has been a need for improvements.

For example, conventional synthetic methods require complicated steps for protection and deprotection of a protecting group in the amino acid and produce a high level of impurities, as well as often leading to the creation of racemic mixtures containing different enantiomeric forms of the peptide from which the desired form must often be separated and purified.

Standard purification procedures are very expensive and in some cases render it commercially unsupportable to make a peptide-based drug using conventional synthesis methods.

Now researchers at Ajinomoto's AminoScience unit have discovered a novel enzymatic method for the industrial production of peptides, and are using it initially to make alanylglutamine, a peptide with beneficial effects on immune function that to date has not been developed commercially because of the prohibitively high cost of its manufacture.

In the new method, the amino acid is esterified, and this ester is enzymatically coupled with another amino acid. The approach can be used not only to synthesise dipeptides and oligopeptides, but also longer peptides including non-native types.

Ajinomoto said it has already set up production-scale systems based on the new technology, and will launch alanylglutamine as the first product in the spring of 2005. It estimates that the potential market scale for the alanylglutamine is estimated at about 200 tonnes worldwide.