Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A clear view through trees

29.11.2010
Large tree-like sugar clusters provide potential in vivo probes for cancer cells

Challenges in isolating and synthesizing protein-bound sugar molecules called N-glycans, which help stabilize insulin levels and modulate antibody-dependent immune responses among many other important processes in the body, has limited the investigation of their function and interaction with cultured cells and dissected tissues.

Now, a team led by Yasuyoshi Watanabe and Satoshi Nozaki from the RIKEN Center for Molecular Imaging Science (CMIS), Kobe, has developed the first series of fluorescent and radioactive probes to track these molecules in living animals, which may eventually be used to track tumors¹.

According to Nozaki, N-glycans, which contain sialic acid residues, always form clusters in vivo allowing them to maximize their interactions and selectivity towards N-glycan-binding proteins and other biomolecules. “It is rather rare that a single molecule of N-glycan shows significant biological activity,” he says.

To recreate these in vivo conditions, the researchers worked in close collaboration with Katsunori Tanaka from Osaka University to attach up to 16 sugar molecules to branched lysine oligopeptides, creating the largest tree-like oligosaccharide cluster ever prepared (Fig. 1). After linking the clusters to fluorescent and radioactive labels, they injected the resulting probes into the tail vein of immunodeficient mice.

Positron emission tomography (PET) imaging showed that the number of glycans in the clusters determined their lifetime in vivo. Four- and eight-sugar clusters rapidly disappeared through the kidney in just one hour. Clusters containing 16 N-glycans, however, remained in the body for over four hours before being eliminated through the kidney and the gallbladder—a desirable feature when studying how N-glycans travel in living subjects.

Furthermore, the team discovered that differences in the way the sialic acids are connected to the N-glycans influenced cluster behavior and build up in specific organs. The so-called (2–6)-linked sialic acids stabilized the clusters in serum, leading to their accumulation in the liver through interactions with specific protein receptors. In contrast, their (2–3)-linked congeners rapidly cleared through the bladder. Also, fluorescence imaging revealed that clusters bearing both types of linkages were most fluorescent in the spleen, suggesting their capture by a part of the immune system called the reticuloendothelial system.

The researchers hope to use these clusters as molecular probes for tumors. They are also planning to prepare clusters consisting of three to four different glycans in order to enhance the selectivity of the probes toward tumors and specific organs. “Nobody has done it, but the data shows that we can achieve it,” says Nozaki.

The corresponding author for this highlight is based at the Molecular Probe Dynamics Laboratory, RIKEN Center for Molecular Imaging Science

Journal information

Tanaka, K., Siwu, E.R.O., Minami, K., Hasegawa, K., Nozaki, S., Kanayama, Y., Koyama, K., Chen, W. C., Paulson, J. C., Watanabe, Y. & Fukase, K. Noninvasive imaging of dendrimer-type N-Glycan clusters: in vivo dynamics dependence on oligosaccharide structure. Angewandte Chemie International Edition 49, 8195–8200 (2010).

gro-pr | Research asia research news
Further information:
http://www.rikenresearch.riken.jp/eng/research/6453
http://www.researchsea.com

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

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...

Im Focus: Breaking: the first light from two neutron stars merging

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....

Im Focus: Smart sensors for efficient processes

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...

Im Focus: Cold molecules on collision course

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...

Im Focus: Shrinking the proton again!

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>