In June 2008, University of Oregon chemist Shih-Yuan Liu reported in the Journal of the American Chemical Society his lab's synthesis of boron-nitrogen compounds with electronic and structural similarities to fundamentally important benzene molecules. That synthesis suggested a new tool for possible use in biomedical research as well as in materials science.
What Liu's lab created were benzene surrogates known as 1,2-dihydro-1,2-azaborines that possess electron-delocalized structures consistent with aromaticity -- a core concept in chemistry where rings of atoms exhibit unexpected stability.
Now, in the Sept. 1 issue of Angewandte Chemie, a weekly journal of the German Chemical Society, Liu and colleagues show that their synthesized compounds indeed are accepted in non-polarized hydrophobic pockets of a well-studied enzyme, a member of the lysozyme family discovered by Alexander Fleming in 1921 and used widely in biomedical research.
The "proof of concept" was completed in the Institute of Molecular Biology lab of the UO physicist Brian W. Matthews, where Liu's synthesized compound was treated with T4 lysozymes, crystallized and examined with high-resolution X-ray crystallography.
"I feel this is a fairly big step forward," Liu said. "Our compounds bind efficiently to the T4 lysozyme and behave as hydrophobic arene molecules similar to natural systems. Our compound actually has polar features, so it was questionable that it would bind to the enzyme's hydrophobic pocket, but it did and very similarly to the way carbon molecules would bind."
In essence, Liu and colleagues have potentially put boron, a commonly occurring essential nutrient in plants -- but seemingly "bypassed by nature in evolution" of other living things, Liu said -- into play as an alternative to carbon in manufacturing target-specific pharmaceuticals. The use of boron in the biomedical field is not new but its acceptance has been hampered by instability, but interest has risen in the last decade, Liu said.
An analysis of boron's medical potential appeared in the February issue of EMBO Reports. Boron is being studied by a number of drug manufacturers. It currently is used as an antibacterial drug component and as part of a therapy for multiple myeloma. The advance by Liu's lab strengthens the case that boron-based molecules can be used as new pharmacophores, or as markers of drugs in living tissue, and to improve long-stymied attempts to develop boron-neutron capture therapies to produce inhibiting agents for cancer treatment.
"This research provides the first experimental evidence that enzymes in our bodies cannot distinguish between our artificial compound versus the all-carbon systems," Liu said. "We can trick the enzymes to believing they are accepting the real thing."
The National Institutes of Health funded the research. Co-authors were Liu's chemistry doctoral student Adam J.V. Marwitz, Matthews and Lijun Liu, a research associate in the Matthews lab.About the University of Oregon
Source: Shih-Yuan Liu, assistant professor of chemistry, 541-346-5573; firstname.lastname@example.orgLinks:
Jim Barlow | Newswise Science News
Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.
Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
12.12.2017 | Physics and Astronomy
12.12.2017 | Earth Sciences
12.12.2017 | Power and Electrical Engineering