Saturday, May 7, 2011

Natural protection against radiation

In the midst of ongoing concerns about radiation exposure from the Fukushima nuclear power plant in Japan, scientists are reporting that a substance similar to resveratrol — an antioxidant found in red wine, grapes and nuts — could protect against radiation sickness. The report appears in ACS Medicinal Chemistry Letters.

Michael Epperly, Kazunori Koide and colleagues explain that , either from accidents (like recent events in ) or from radiation therapy for cancer, can make people sick. High doses can even cause death. The U.S. Food and Drug Administration is currently evaluating a drug for its ability to protect against radiation sickness, but it is difficult to make in large amounts, and the drug has side-effects that prevent its use for cancer patients. To overcome these disadvantages, the researchers studied whether resveratrol — a natural and healthful antioxidant found in many foods — could protect against radiation injuries.

They found that resveratrol protected cells in flasks but did not protect mice (stand-ins for humans in the laboratory) from radiation damage. However, the similar natural product called acetyl resveratrol did protect the irradiated mice. It also can be produced easily in large quantities and given orally. The authors caution that it has not yet been determined whether acetyl resveratrol is effective when orally administered.

More information: “The Use of 3,5,4’-Tri-O-acetylresveratrol as a Potential Prodrug for Resveratrol Protects Mice from gamma-Irradiation-Induced Death” ACS Medicinal Chemistry Letters.

Provided by American Chemical Society (news : web)

Cola detectives test natural flavoring claims for pricey soft drinks

Scientists are reporting development and successful testing of a new way to determine whether cola drinks -- advertised as being made with natural ingredients and sold at premium prices -- really do contain natural flavoring. The report appears in ACS' Journal of Proteome Research.

In the study, Pier Giorgio Righetti and colleagues explain that cola drinks purportedly made from natural cola nuts are becoming popular and are sold in many natural food stores. Genuine cola "nuts" are seeds from the fruit of the cola tree, which is native to African rainforests, and they are expensive to harvest and ship. In West African cultures, people include the nuts in ceremonies and offer them to guests. The nuts also have possible — they may help treat whooping cough, asthma, migraines and dysentery. Most soft drink manufacturers don't use cola nuts today, but a select few are starting to advertise cola as a natural ingredient in their products — and charge extra for it. To see whether consumers are getting what they pay for, the scientists set out to find a way to finger the drinks with real natural extracts.

The group found that testing for proteins was an accurate way to verify natural flavoring claims. They detected plant proteins in a drink claiming to have "organic agave syrup and cola nut extracts". On the other hand, Coca Cola products — which do not claim to include extract — have no protein. The scientists say, "The identifications here obtained represent the quality mark of this beverage and, in a way, give a certificate of authenticity."

More information: “Going nuts for nuts? The trace proteome of a Cola drink, as detected via combinatorial peptide ligand libraries” Journal of Proteome Research.

Provided by American Chemical Society (news : web)

Simulating amyloid formation

Many neurodegenerative diseases are characterized by proteins that assume an abnormal configuration, which leads to their aggregation and deposition in and around rve cells, causing cell death. This process, called amyloid formation, is a common pathological feature in diseases such as Alzheimer’s, Parkinson’s and prion diseases, as well as type II diabetes. Charlotte Hauser and co-workers from the A*STAR Institute of Bioengineering and Nanotechnology and Institute of High Performance Computing along with colleagues in Europe have now designed a class of ultrasmall peptides that simulate the self-assembly of abnormally folded proteins in such neurodegenerative conditions.

Hauser and her co-workers designed ultrasmall consisting of three to six amino acid residues, each containing a characteristic motif—a ‘tail’ of uncharged residues with decreasing affinity to water capped by a polar ‘head’ residue. These peptides spontaneously self-assembled in water to form fibril structures (pictured) resembling those that make up the amyloid-ß plaques found in the brains of Alzheimer’s patients.

The researchers hypothesize that fiber assembly is a complex stepwise mechanism involving at least three distinct stages. Individual peptide molecules first bond to each other in an anti-parallel arrangement to form dimers. The pairs then line up to form single ?-helical fibers as intermediate structures, which continue to assemble and then condense into fibrous scaffolds in the form of solid hydrogels.

The team further examined the driving forces for self-assembly and found that gel formation was critically dependent on the length of the tail and the polar nature of the head. Peptides containing six amino acid residues formed gels more readily than the others, and the strongest gels were formed by peptides containing an acidic head residue. A minimum peptide concentration was required for fiber formation, and increasing the temperature was found to accelerate the self-assembly process.

Investigation into the assembly process and experimental results were verified by computer simulations. This helped the research team confirm that the formation of peptide pairs precedes fiber formation, suggesting that the peptides have a strong tendency to aggregate because the sheet-like structures have a lower free energy state than individual fibers, and are therefore more stable.

“Understanding the driving forces that enable these ultrasmall peptides to stably self-assemble into macromolecular structures will shed light on aggregate formation in amyloidogenesis,” says Hauser. “This would facilitate the design of new therapeutics to prevent and control plaque formation in neurodegenerative disorders and a wide range of other debilitating diseases.”

More information: Hauser, C. A. E. et al. Natural tri- to hexapeptides self-assemble in water to amyloid ß-type fiber aggregates by unexpected ?-helical intermediate structures. Proceedings of the National Academy of Sciences 108, 1361–1366 (2011). … s.1014796108

Many fatal neurodegenerative diseases such as Alzheimer’s, Parkinson, the prion-related diseases, and non-neurodegenerative disorders such as type II diabetes are characterized by abnormal amyloid fiber aggregates, suggesting a common mechanism of pathogenesis. We have discovered that a class of systematically designed natural tri- to hexapeptides with a characteristic sequential motif can simulate the process of fiber assembly and further condensation to amyloid fibrils, probably via unexpected dimeric ?-helical intermediate structures. The characteristic sequence motif of the novel peptide class consists of an aliphatic amino acid tail of decreasing hydrophobicity capped by a polar head. To our knowledge, the investigated aliphatic tripeptides are the shortest ever reported naturally occurring amino acid sequence that can adopt ?-helical structure and promote amyloid formation. We propose the stepwise assembly process to be associated with characteristic conformational changes from random coil to ?-helical intermediates terminating in cross-ß peptide structures. Circular dichroism and X-ray fiber diffraction analyses confirmed the concentration-dependent conformational changes of the peptides in water. Molecular dynamics simulating peptide behavior in water revealed monomer antiparallel pairing to dimer structures by complementary structural alignment that further aggregated and stably condensed into coiled fibers. The ultrasmall size and the dynamic facile assembly process make this novel peptide class an excellent model system for studying the mechanism of amyloidogenesis, its evolution and pathogenicity. The ability to modify the properties of the assembled structures under defined conditions will shed light on strategies to manipulate the pathogenic amyloid aggregates in order to prevent or control aggregate formation.

Provided by Agency for Science, Technology and Research (A*STAR)