Glycotechnology Laboratory
Mitsubishi Kagaku Institute of Life Sciences (MITILS)
Glycotechnology Laboratory
Mitsubishi Kagaku Institute of Life Sciences (MITILS)
Glycoconjugates existing on cell surfaces play important roles in development, immunity, and as ligands of various molecules. Our research objective is to investigate the chemical information contained in carbohydrates at the molecular level.
A proof of no anomerization in gas phase.
Carbohydrates isomerizes in water. This is called anomerization. The ring of an hemiacetal opens to form an aldehyde in the presence of water and closes again forming a cyclic hemiacetal again. During the process, configuration of hydroxyl group at the anomeric position epimerize. This phenomenon was discovered by Dubrunfaut in 1846 about 50 year before Fisher received the Nobel prize.
In the 19th century, sugar was one of the major merchandise that of course lead to profit. How SWEET! The sugar chemistry was active in connection to the economical situation. The polarimeter was used for the quality control purpose leading to the discovery of mutarotation caused by the anomerization process.
We are investigating the detail chemical events taking place during the collision-induced dissociation (CID) reactions inside the mass spectrometer. We took a sodiated hemiacetal species and analyzed the behavior of the ion by the energy-resolved mass spectrometry in the stage-discriminated manner. We found that the sodiated hemiacetals do not anomerize in gas phase. This is fundamentally important as the basis of methods based on CID, because the type of ion species retain the anomeric configuration originated in their precursors thus one can get information about the configuration of a particular glycosidic linkage of oligosaccharide.
Based on this finding, we showed that 1) mutarotation process can be monitored by mass spectrometry and 2) possibility in investigating a mechanism of glycosidase reactions (stereo-inversion vs. retention).
We developed a novel method named as Stage-Discriminated Correlation) to reveal whether an totally unknown oligosaccharide (not limited to though) sample is “pure” or not. The basis of this is the individual chemical entities carry a characteristic activation energies, which can be observed by the energy-resolved mass spectrometry technique.
Stereospecific synthesis of hemiacetals in gas phase
Stereospecific generation of individual anomers of hemiacetals in gas phase: A first acomplishment
Aminobutyl alpha- and beta-glycosides of lactose were individually subjected to collision-induced dissociation conditions to produce hemiacetal and pyrollidine. The generated hemiacetal was found to have the stereochemistry retained.
Blockbuster Paper
Papers with sum of number of citations during continuing five years exceeding 50 is called blockbuster paper.
Carbohydrate Research, 1993, 243, 139-164.
8 times (1999-2006)
Journal of the American Chemical Society, 1994, 116, 12073-12074.
10 times (2000-2009)
Angewandte Chemie International Edition, 1996, 35, 2510-2512.
4 times (2002-2005)
Angewandte Chemie International Edition, 1998, 37, 1524-1528.
3 times (2005-2007)
These papers have very long life that pleases me, but it takes at least six years to be evaluated. This is critical in the current evaluation system. People will be fired before it is acknowledged by others. We might try strategically publish short-live high impact papers as well. Well, what a hell. I matters but I do not care.
Chemoinformatics:
a missing view point
Structural information contained in a combinatorial library:
Combinatorial chemistry has been a focus area in connection with drug discovery in pharmaceutical companies. The definition of the term is the method of creating a series of compounds using multiple components, of which numbers greater than two, in a way of combination. A set of compounds created in this manner is called a combinatorial library. The term combinatorial chemistry is often used together with a following high-throughput screening, thus it is thought to speed-up a process of finding seed compounds through generation of diverse compounds and the screening.
Despite the advantage of the method, it is ignored that the structural information contained in the generated diverse compounds. Such information will be extremely useful in structural analysis, structure-activity relationship, etc. These are buried and the compounds found out to be non-active is dumped. In this manner, structurer-activity relationship is discussed only for the hit compounds where the definition of hit is generally biased. Chemoinformatics thus has a fundamental problem.
One may say “Well, what is wrong? This is the definition.” This is true, but it is also true that a value of structural information in the diversity is missed. We can find such value in synthesized compounds. The problem probably associates with the situation that the current science is so dependent on commercialism and so we do not get enough time for the research. Commercialism may be tolerated but the issue is the time. Is our efforts for tomorrow, day after tomorrow, or ... It seems we are allowed to do things for tomorrow only. This is the problem.
Home Page renewal open
Our institute will be closed in about one and half years. At this time, I thought about many things and decided to update our home page to remind myself feelings when I started research at the institute in 1999. Unfortunately however, I am experiencing an emergence of some antisocial thoughts in my mind.
It is quite curious that there is still budget maintaining garden despite the fact that we are forced to be out.
Evaluation!?
Total citation in 2006 was 100 by SCOPUS and thank who cited our articles.
Cover story included as “Libraries not of books but of oligosaccharides have potentially important applications in medicine and the pharmaceutical industry. However, the building of these libraries is hindered by lengthy protocols and specific reaction conditions that cannot be applied generally. In response to these issues, Kanie and co-workers developed an efficient synthetic strategy based on a combination of solid-phase reaction and orthogonal glycosylation, in which monosaccharides are coupled to each other step by step to form anomeric combinations of oligosaccharides.”.
We synthesized a library of linear trisaccharides where we decided to adopt stereo-non-selective glycosylation at each glycosylation site on acceptor molecules.
-----Related articles-----
(German edition: Angew. Chem. 2006, 118, 3935-3938.)
July 30 2007 Cover, Vol. 85, Issue 31
C&EN NEWS
The Carbohydrate Connection
Hello and Goodbye
Research focus
Combinatorial Chemistry
Trisaccharide library synthesis
Functional Analysis
Azasugars and other probes
Structural Analysis
Mass spectrometry
Microchip
Simulation of biological functions
Links
International Carbohydrate Symposium 2010 in Tokyo
Trends in Glycoscience and Glycotechonoly
The Japanese Society of Carbohydrate Research
The Mass Spectrometry Society of Japan
IUPAC (International Union of Pure and Applied Chemisty)
Mitsubishi Kagaku Institute of Life Sciences (MITILS)
Thank you very much for visiting the site, however, we no longer work here any more. Actually, our institute came to an end of existence today on March 31, 2010.
Our brand new projects is going to be carried out at a new location at RIKEN institute.