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 Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>