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
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
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering