Chemists show that nature could have used different protein building blocks

Feb 05, 2007
Beta-Bundles -- Ribbon Diagram Representations of a Beta-Peptide Bundle
Beta-Bundles: Ribbon diagram representations of a beta-peptide bundle illustrating packing between helices and within the hydrophobic (green) core. Credit: Schepartz/Yale

Chemists at Yale have done what Mother Nature chose not to — make a protein-like molecule out of non-natural building blocks, according to a report featured early online in the Journal of the American Chemical Society.

Nature uses alpha-amino acid building blocks to assemble the proteins that make life as we know it possible. Chemists at Yale now report evidence that nature could have used a different building block – beta-amino acids — and show that peptides assembled from beta-amino acids can fold into structures much like natural protein.

Beta-Bundles -- Ribbon Diagram Representations of a Beta-Peptide Bundle
Beta-Bundles: Ribbon diagram representations of a beta-peptide bundle illustrating packing between helices and within the hydrophobic (green) core. Credit: Schepartz/Yale

"The x-ray structure featured in the report shows a molecule that shares many of the structural characteristics of natural proteins," said principal author Alanna Schepartz, the Milton Harris '29 Ph.D. Professor of Chemistry at Yale and a Howard Hughes Medical Institute Professor. "Related studies show that the physical properties of the molecule are also remarkably similar to natural proteins. In other words, the beta-peptide assembly looks and acts a lot like a real protein."

The ability to mimic natural proteins makes beta-peptides powerful new tools for basic research and drug discovery. Like a taped recording, their greatest value may be in their difference from a live performance.

"Since beta-peptides are not processed in the cell like natural peptides or proteins, it may be possible in the future to design beta-peptides that perform better or in more locations than current protein drugs," said Schepartz. "They also may have unique properties as biomaterials."

Natural proteins are composed of linear chains of alpha-amino acids. Beta-peptides are composed of beta-amino acids, which have an extra carbon in their backbone. Like alpha-amino acids, beta-amino acids are generated under simulated pre-biotic conditions, are isolated from meteorites, and are byproducts of metabolism, but they are not genetically encoded like natural proteins, nor are they built into chains by cells.

Since the early 1990's, scientists have been able to assemble beta-peptides into isolated helices. Until now, however, creating a structure that mimics the larger size and complex folded architecture of a natural protein had been an elusive goal. Schepartz's team solved the dilemma by designing a molecule that could form a bundle using characteristics found in natural proteins — a greasy interior that repels water and a water-friendly exterior. This paper, which provides the first high-resolution picture of such a structure, shows a bundle of eight beta-peptides.

"The structure we see is intriguing, as it suggests that natural proteins could have been composed of beta-amino acids, but were not chosen to do so," said Schepartz.

Citation: J. American Chemical Society, ASAP Article DOI:10.1021/ja068678n (January 19, 2007)

Source: Yale University

Explore further: Science to the rescue of art

add to favorites email to friend print save as pdf

Related Stories

Tracing water channels in cell surface receptors

31 minutes ago

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in our cells, involved in signal transmission across the cell membrane. One of the biggest questions is how a signal recognized at the extracellular ...

Seeing protein synthesis in the field

22 hours ago

( —Caltech researchers have developed a novel way to visualize proteins generated by microorganisms in their natural environment—including the murky waters of Caltech's lily pond, as in this ...

Scientists map protein in living bacterial cells

Sep 04, 2014

( —Scientists have for the first time mapped the atomic structure of a protein within a living cell. The technique, which peered into cells with an X-ray laser, could allow scientists to explore ...

Nano-forests to reveal secrets of cells

Sep 02, 2014

Vertical nanowires could be used for detailed studies of what happens on the surface of cells. The findings are important for pharmaceuticals research, among other applications. A group of researchers from ...

Recommended for you

Chemical biologists find new halogenation enzyme

4 hours ago

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

9 hours ago

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

9 hours ago

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

Decoding 'sweet codes' that determine protein fates

11 hours ago

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of ...

Science to the rescue of art

Sep 14, 2014

Vincent van Gogh's "Sunflowers" are losing their yellow cheer and the unsettling apricot horizon in Edvard Munch's "The Scream" is turning a dull ivory.

User comments : 0