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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>