Zwit-1F, an unnatural protein created by reseachers at Yale University. According to the team, proteins like Zwit-1F could be useful in designing drugs because they won't be degraded by the body's immune system.
Credit: Douglas S. Daniels
SYDNEY: A new 'unnatural' protein could pave the way for drugs which are more effective than those based on natural molecules, according to U.S. researchers.
A team from Yale University in Connecticut have constructed a complex, stable protein out of amino acids not found in any natural protein. Their findings could help scientists design drugs that look and act like real proteins but won't be degraded by enzymes or targeted by the immune system, as natural proteins are.
Proteins - complex molecules found in all living organisms - are made up of amino acids. The order of amino acids in a protein determines how the protein is shaped and dictates the functions it can perform. Though in theory there are nearly an unlimited number of possible amino acids, according to scientists the proteins of all life on Earth are made up of the same 20.
The U.S. team, led by Alanna Schepartz, built the new short protein, or peptide, from beta-amino acids, which, although they exist in cells, are never found in proteins. Beta-amino acids differ from the alpha-amino acids that compose natural proteins by the addition of a single chemical component into each amino acid's structure.
"The fundamental insight from this study is that beta-peptides can assemble into structures that generally resemble natural proteins in shape and stability," said Schepartz. She added that the team's finding, reported in the Journal of the American Chemical Society, is the first step towards creating more complex unnatural proteins that possess true biological function.
To biochemists, a protein's chain-like amino acid sequence is considered its primary structure. Its secondary structure is produced when this chain folds, forming characteristic shapes such as helices and sheets. The three-dimensional arrangement of these shapes gives a protein what is known as its tertiary structure. Each of these levels of organisation is crucial to determining a protein's function.
In previous studies, researchers had shown that beta-peptides could fold from their chain-like primary structure into more complex secondary structures. But these synthetic proteins adopted very little or poorly defined tertiary structure, and no one had yet shown that a beta-peptide could self-assemble into the kinds of stable bundles of spiral-shaped helices that are characteristic of natural proteins, Schepartz said.
While the new protein comes far nearer to mimicking natural proteins, according to Schepartz there are still some significant differences between the new protein and those found in nature.
One of the most exciting potential results of the team's finding could be design of beta-peptide drugs. "There is growing interest in proteins as drugs," said Schepartz. "And although certain proteins are very effective pharmaceuticals, protein drugs generally suffer from storage and stability problems outside the body and from degradation inside the body. Beta-peptides may be more stable than traditional protein drugs and would not be recognised by the [enzymes] that destroy proteins in the cell."
Schepartz said their discovery that the beta-peptide structurally resembles natural peptides raises a thorny biological question: why don't these proteins exist in nature?
"Certain beta-amino acids are naturally synthesised in cells, and they are even loaded onto transfer RNA molecules that carry the amino acid components to the protein-making machinery of the cell, the ribosome," she noted. "But to my knowledge, there are no ribosomally constructed proteins that contain beta-amino acids," she said.
"The most provocative finding of this paper is that beta-amino acids were not avoided as the building blocks of proteins because they cannot assemble into complex structures," she said. "We've shown that clearly they can."
with the Howard Hughes Medical Institute
Unjustified Fears?
Somehow, Frankenstein's monster comes to mind when reading this article.
Evolution has seemingly avoided creating these combinations on this planet, and life here has, according to the article, no resistance to them.
What happens to the body if these are introduced into it? Would they be the catalyst for unexpected changes?
How easily could these new proteins be released into the environment, and what would be the consequences?
Prions are considered unnatural, and we already know that they can cause serious disease.
I am not against progress, but I hope safety is considered when going further with this research.
polypeptides
Actually, there are a nearly unlimited amount of polypeptide chains, which make up proteins, and only a small number of amino acids, comparatively.
I'm not sure what you mean
I'm not sure what you mean by "only a small number of amino acids." Life on earth primarily only uses 20 kinds (with a few exceptions), but there are a lot more than 20. As the article states, there are essentially an unlimited number of amino acids. To qualify as an amino acid, a molecule simply needs an amine group, a carboxylic acid group, and an arbitrary R group, where R can really be any organic group. It is that arbitrary R group which makes the number of possible amino acids essentially unlimited.