10/21/2009
Designing Aptamers to Control Chemical Reactions
The Science
Aptamers are short single stranded molecules made up of nucleic acids (RNA and DNA) or peptides that bind, like antibodies, to specific target molecules. However, unlike antibodies they can be completely engineered and synthesized in a test tube for a variety of functions. Marit Nilsen-Hamilton’s research group at the Ames Laboratory has led to a new approach for controlling metabolic pathways using aptamers. They discovered that it is possible to develop aptamers, using computational modeling of the aptamer structure, that completely protect target molecules from chemical modification. These results suggest that aptamers might be engineered for use inside cells to alter the flow of chemicals through metabolic pathways with the potential to alter plants or microbes for improved production of biofuels.
Summary
As short nucleic acids, aptamers in solution are believed to be structurally flexible. Consistent with this view, most aptamers examined for this property have been shown to bind their target molecules by mechanisms that can be described as “induced fit”. Using the malachite green aptamer (MGA) as a model system, researchers show that the MGA can protect its bound target, malachite green (MG), from oxidation over several days. These results show that a nucleic acid aptamer can control access to specific chemical groups on its target, which suggests that aptamers might be applied for selectively protecting small molecules from modification.
Principal Investigator
Marit Nilsen-Hamilton
Iowa State University
BER Program Manager
Paul Sammak
U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]
References
Wang, T., J. A. Hoy, M. H. Kamm, and M. Nilsen-Hamilton. 2009. “Computational and Experimental Analyses Converge to Reveal a Coherent Yet Malleable Aptamer Structure That Controls Chemical Reactivity,” Journal of American Chemical Society 131, 14747-55. DOI:10.1021/ja902719q.