Angewandte Chemie International Edition

Cover image for Vol. 56 Issue 6

Editor: Peter Gölitz, Deputy Editors: Neville Compton, Haymo Ross

Online ISSN: 1521-3773

Associated Title(s): Angewandte Chemie, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemistryOpen, ChemPhotoChem, ChemPlusChem, Zeitschrift für Chemie

For full article and contact information, see Angew. Chem. Int. Ed. 1999, 38 (9), 1223 - 1226

Beta lasts longer

Medicines made from synthetic amino acids
get the better of digestive enzymes

Amino acids are the basic building blocks of the proteins that Nature uses to produce muscles, skin, and hair, as well as hormones. Synthetic amino acids, which differ from their natural counterparts only by a single atom, can be used to make hormones that act in a similar way to the "real" hormones. They also better withstand the digestive enzymes in the mouth and stomach, which destroy many conventional medicines too quickly.

All proteins in humans and other organisms are assembled from 20 different amino acids. These all have a comparable composition: they consist of a short main section that contains the necessary elements for linking, and an "attachment" made of different chains of atoms, which vary from amino acid to amino acid. These provide the diversity for the "menagerie" of amino acids. Common to all amino acids, however, is the location at which these chains are attached to the base unit.

Using chemical methods, it is nonetheless possible to move these attachments: if one lets them move a bit further by inserting an additional carbon atom in the base unit, beta-amino acids are formed rather than the natural alpha-amino acids. These can also be used to make protein-like molecules, which amazingly resemble their "real" counterparts.

Dieter Seebach and his co-workers at the Laboratory of Organic Chemistry of the ETH in Zurich, in collaboration with the Swiss firm Novartis Pharma AG, have tried to determine whether hormones can be made out of the beta-amino acids, which would have a similar effect to the natural compounds made of alpha-amino acids. This was successful: the outer shape of a small molecule made from four of these altered building blocks so closely resembled a section of the hormone somatostatin that it was recognized by real somatostatin receptors in an experiment.

The effect of the new hormone actually lagged behind that of the "original" - but the effort may still be worthwhile: for example, because digestive enzymes start breaking down "normal" proteins in the stomach and intestines, many vaccines and hormones must still be directly injected into the bloodstream. The substitutes made of beta-amino acids are not affected by these digestive enzymes - if Seebach's concept stands the test of time, in the distant future it may be possible to leave vaccine or insulin shots in the cupboard.