Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery might improve design, effectiveness of anti-cancer drugs

19.10.2004


Working with an enzyme that degrades anti-cancer drugs in humans, University of North Carolina at Chapel Hill biochemists and colleagues have made a discovery that they believe eventually could help improve such drugs’ design and effectiveness.



The scientists have shown that the enzyme protein can be made to "fly through the vapor phase" -- from which solvent water is totally absent -- without changing its structure.

When a solution containing the enzyme was introduced as a fine spray into a vacuum created in a mass spectrometer in the laboratory, normal solvent molecules were completely evaporated, leaving bare, charged molecules known as ions, the researchers said. The protein ions were trapped in the extremely high vacuum for seconds, but in the new experiments, a single water molecule remained undisturbed, which was a surprise since no one ever saw that before. "This suggests how we might change an inhibitor molecule to make it fit the enzyme more perfectly and hence be more effective in blocking that enzyme’s action in destroying anticancer drugs," said Dr. Richard V. Wolfenden, Alumni Distinguished professor of biochemistry and biophysics at the UNC School of Medicine.


The experiments involving the enzyme cytidine deaminase, which is derived from bacteria and many other sources, mark the first time that scientists have detected a water molecule inside a protein molecule by mass spectrometry, he said. A report on the research appears in the latest issue of the Proceedings of the National Academy of Sciences. Besides Wolfenden, UNC participants include lead author Dr. Christoph H. Borchers, assistant professor of biochemistry and biophysics and faculty director of the UNC Michael Hooker Proteomics Core Facility, and doctoral student Gottfried K. Schroeder. Wolfenden and Borchers are members of UNC’s Lineberger Comprehensive Cancer Center.

"When the active site of this enzyme binds to what is called the active site of a well-fitting inhibitor molecule, it also binds a single water molecule, which appears to be trapped in a small gap left by the inhibitor," Wolfenden said. "The sequestering of the water molecule from its surroundings is evident from the fact that this protein ‘water bottle’ flies for many seconds through a nearly perfect vacuum into which the water molecule would evaporate instantly if it were exposed to the surroundings."

Inside the mass spectrometer manufactured by Bruker Daltronics, Inc., the vacuum was comparable to the vacuum found in intergalactic space, he said. Wolfenden said the presence of the water-filled gap hints at how an inhibitor might be improved further -- by expanding it to fill the gap -- which is important in designing drugs. "Moreover, this specific enzyme is known to inactivate the anticancer agent cytarabine," he said. "That inactivation limits the effectiveness of cytarabine in cancer tissue such as in non-Hodgkins lymphoma, several forms of leukemia and other cancers. By protecting cytarabine against degradation, a powerful inhibitor of the enzyme cytidine deaminase might be used in combination with cytarabine for cancer chemotherapy." The UNC scientists are now exploring that possibility in further laboratory studies, Wolfenden said.

Since it is highly sensitive and accurate, mass spectrometry is a major analytical tool capable of sequencing peptides and allowing researchers to identify and characterize proteins at their physiological level. The instrument in which the experiments were performed is located at the North American headquarters of Bruker Daltonics in Billerica, Mass.

The Michael Hooker Proteomics Core Facility will soon acquire one of the sophisticated mass spectrometers, said Borchers, also a member of UNC’s Center of Environmental Health and Susceptibility.

Other authors of the new paper are Dr. Victor E. Marquez of the National Cancer Institute, Dr. Steven A. Short of GlaxoSmithKline, Dr. Mark J. Snider of the College of Wooster, and Dr. J. Paul Speir of Bruker Daltonics.

The National Institutes of Health supported the research.

David Williamson | EurekAlert!
Further information:
http://www.med.unc.edu

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

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...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

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,...

Im Focus: Towards data storage at the single molecule level

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>