This is because unlike most other proteins, transferrin can cross the blood-brain barrier. But a new study of transferrin and its receptor by chemists at the University of Massachusetts Amherst reveals that transferrin isn’t as open to drug loading as hoped, so creating a good delivery system may be more challenging than previously thought.
Nevertheless, work led by UMass Amherst researcher Igor Kaltashov and doctoral student Rachel Leverence, now at the University of Wisconsin-Madison, with Anne Mason of the University of Vermont College of Medicine, highlights for the first time the great potential of the mass spectrometry method they used in this study, for providing precise details of complex protein-receptor interactions under conditions that closely mimic those inside the body. Their findings appear in the current online edition of Proceedings of the National Academy of Sciences.
As Kaltashov explains, “Our research looked at how the transferrin protein interacts with its receptor and how this has relevance for anti-cancer therapy.” One reason medical researchers have been so hopeful about transferrin and its drug-delivery potential is that cancer cells demand huge amounts of iron to thrive. Scientists long believed that after the transferrin protein delivered its iron load into a cell, it would emerge again not bound to the receptor, leaving a space for drug uptake and delivery into the tumor cell, thus providing a way to introduce toxins to kill the cancer.
“But we found that life is much more complicated,” says Kaltashov. “One of our important conclusions is that transferrin would probably interfere with the binding between the receptor and any anti-cancer drug one might try to attach.” Despite this, his findings do not represent a dead end, the analytical chemist adds. The mass spectrometry technique was extremely effective in allowing the researchers to observe and examine the transferrin receptor complex and its behavior in detail. The method is generalizable and can be applied to any system, including potential new anti-cancer drugs, Kaltashov adds.
Specifically, he and colleagues used an ion cyclotron resonance mass spectrometer, a cross-over between more familiar medical magnetic imaging devices such as MRI and classical mass spectrometers. It is powerful enough to analyze proteins, DNA and other biological molecules. First the ions, the electrically charged forms of molecules, are extracted from a fine aerosol produced by spraying solutions containing biomolecules. These ions are then guided to a magnet through a system of ion optics under ultra-high vacuum conditions.
Once inside the magnet, the ions move along circular orbits; the frequency of this movement provides very precise information on molecular masses. This new type of instrument is so powerful it can measure the mass of nano-objects ranging from single atoms to giant biomolecules with precision better than 0.0001 percent, the chemist says.
Further, the Kaltashov laboratory recently purchased a powerful new mass spectrometer with an $800,000 Major Research Instrumentation grant from the National Science Foundation to aid research in life sciences, where knowledge of molecular structure is critical for understanding processes as diverse as drug delivery and protein folding. Thus the UMass Amherst campus now has one of the best equipped mass spectrometry laboratories in the nation.
As Kaltashov explains, the usefulness of such mass spectrometers to life sciences research extends far beyond simply measuring atomic and molecular masses. For example, one can break a large molecule apart inside the instrument and measure masses of the resulting fragments. “Figuring how these fragments may fit together in pretty much the same way a puzzle is pieced together provides a way to determine the structure of proteins, DNA and other biomolecules,” he says.
Now his group is developing new methods to probe other traits of proteins and their brethren in the biological world, such as three-dimensional organization and interactions with physiological partners. This technology will be critical for advancing knowledge in areas ranging from fundamental problems in biophysics and structural biology to design and testing of new biopharmaceutical products.Igor Kaltashov
Igor Kaltashov | Newswise Science News
Repairing damaged hearts with self-healing heart cells
22.08.2017 | National University Health System
Biochemical 'fingerprints' reveal diabetes progression
22.08.2017 | Umea University
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,...
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...
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...
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...
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...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
22.08.2017 | Health and Medicine
22.08.2017 | Materials Sciences
22.08.2017 | Life Sciences