Ribonucleic acid (RNA) is a biologically important molecule that is very similar to DNA, the blueprint of life. Naturally occurring RNAs, such as transfer RNA (tRNA), contain modified building blocks (“nucleosides”), which are involved in decoding genetic information.
Deazaguanosine nucleosides, in particular, are of significant interest for their antibacterial, antifungal, antiviral, and anticancer activity. In the European Journal of Organic Chemistry, Thomas Carell and his team at Munich's Ludwig Maximilians University (Germany) have now introduced a method to prepare tRNA nucleosides through a novel Turbo-Grignard-based approach with an unprecedented level of control from a common intermediate.
Because of the biological importance of deazaguanosines, a reliable method for their preparation is desirable. In this way, scientists can easily study their functions and the role they play in the treatment of diseases. One of the problems for synthetic chemists, however, is that these compounds often contain various reactive groups at several locations within the molecule. Precise control over the reactivity at a single position can therefore be difficult. Thus, the development of a site-specific reagent is required.
For their synthesis, the authors opted to use the versatile Turbo-Grignard reagent. The “normal” Grignard reagent is used by chemists to introduce a group into a molecule at a reactive site; it consists of the group to be added complexed to the metal magnesium. The Turbo-Grignard is also complexed to a lithium salt, which generally allows reactions to be performed under mild conditions – an important advantage when dealing with biologically relevant compounds.
In their article, the team shows that the Turbo-Grignard reagent has a specific point of attack and that it can be used in the presence of other reactive groups. Importantly, an adjacent group that proved problematic under different conditions was found to be completely unreactive to the turbo reagent, thereby allowing efficient synthesis of the desired nucleosides; the same reaction performed with the “normal” Grignard reagent resulted in decomposition of the desired products. The fact that other reactive groups in the molecule remain untouched facilitates the synthesis of deazaguanosine-derived tRNA nucleosides, which should enable detailed biochemical investigation of their functions in vivo and help in the treatment of genetic diseases.
Author: Thomas Carell, Ludwig-Maximilians-Universität München (Germany), http://www.cup.uni-muenchen.de/oc/carell/
Title: Efficient Synthesis of Deazaguanosine-Derived tRNA Nucleosides PreQ0, PreQ1, and Archaeosine Using the Turbo-Grignard Method
European Journal of Organic Chemistry, Permalink to the article: http://dx.doi.org/10.1002/ejoc.201000987
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Life Sciences
27.10.2016 | Life Sciences
27.10.2016 | Power and Electrical Engineering