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
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Interdisciplinary Research
20.10.2017 | Materials Sciences
20.10.2017 | Earth Sciences