Protein's non-natural alternative

Proteins are formed from chains of alpha peptides. Beta peptides also exist, and behave in much the same way as alpha peptides, but they are rarely found in nature. Beta peptides are of interest because of what they can tell researchers about protein folding in general. Now, chemical biologists at Yale University, US, have built what they say is a ’remarkably protein like’ structure from beta peptides.

The alpha peptides that make up natural proteins are formed by the linking of alpha amino acids. The alpha tag refers to the position at which two components of the amino acid are attached. The amino- and carboxylate groups of an alpha amino acid are attached to the same carbon, the alpha carbon. Beta amino acids are formed when the amino group is attached to a different carbon, the beta carbon. This arrangement is rarely found in nature. Beta peptides hint at numerous future applications because, unlike their alpha cousins, they are stable to proteolytic degradation.

Alanna Schepartz, professor of chemistry at Yale, and her team have built a beta-dodecapeptide that self-assembles spontaneously in aqueous solution into a highly thermostable beta-peptide octamer. They determined its structure by x-ray crystallography.

The work is a rare example of a quaternary structure of a beta peptide, said Per Arvidsson, associate professor in the department of biochemistry and organic chemistry at Uppsala University, Sweden. ’It is also the most well documented as it shows a high-resolution x-ray structure,’ Arvidsson told Chemistry World.

’The main surprise is to see how the packing of beta-peptide helices differs from that of alpha-peptide helices,’ he said. ’The next challenge will be to synthesise a single beta-peptide chain that will adopt a folded tertiary structure.’

The work has no immediate applications, said Arvidsson, but its importance lies in the fact that it challenges current understanding of folding in the natural alpha-protein world.

’It is truly amazing to be able to design protein-like architectures de novo using completely artificial building blocks,’ he enthused. ’As beta peptides are known to be completely stable to proteolytic degradation, future uses in the field of biologically active proteins or catalysts are likely to have a major impact.’

Bea Perks