Chemistry / Bio
Developing and Evaluating a “Tool” to Analyze Life Phenomena
Makoto Hashimoto , Associate Professor
Research Faculty of Agriculture / Graduate School of Agriculture (Department of Applied Bioscience, School of Agriculture)
High school : Obihiro Hakuyou High School (Hokkaido)
Academic background : Graduate School of Pharmaceutical Sciences, Hokkaido University
- Research areas
- Chemical Biology, Synthetic Organic Chemistry
- Research keywords
- organic chemistry, protein, bioactive compound, biomolecule, structure-activity relationship
What are you aiming for?
Compounds that have an effect on organics are generically called bioactive compounds. Although we refer to the compounds used to maintain the biological phenomena of human as “drugs” and the compounds used to destroy the life-sustaining activities of insect pests and weeds as “pesticides,” both of these compounds can be described as bioactive compounds. These bioactive compounds act on biomolecules (proteins and nucleic acids). Understanding the interaction established between bioactive compounds and biomolecules to exert physiological activity may provide important information for developing new drugs and pesticides. There are many ways to analyze these interaction, but our laboratory is working on the development of a technique combining the affinity of bioactive substances with light.
To actually implement such analysis, research at the university needs to combine a range of subjects that are treated separately in high school, ranging from organic chemical (chemical) experiments for derivatizing bioactive compounds (chemical conversion) to biochemical (biological) experiments to examine interaction with the target biomolecule. Our current research activities include the analysis of the interaction between sweet substances and sweet taste receptors. Although various substances are known to offer sweet tastes, there are many unexplained things about how they bind to sweet taste receptors to cause bioactivity. You may know of α-amino acids that have a chiral center in L-form as a component of protein. Their D-form with the opposite chiral center are known to offer a sweet taste.
To study the difference in bioactivity depending on the configuration in joint research with Suntory Holdings and Tokyo University, we synthesize derivatives of one of the α−amino acids, phenylalanine, and study their interactions. We also study interaction of many other sweet substances by derivatizing them by chemical conversion methods using organic chemistry, and in some cases, enzymes. This research corresponds to the basic principal of the Department of Applied Bioscience, School of Agriculture; “Molecular tools for our future” - “Develop molecular tools” and “Clarify life phenomena using the developed tools.” Under these principles, the Department of Applied Biosciences has established an education system that improves students' level of understanding through not only classroom lecture but also it practice. Specifically, in our system, students synthesize and use gene detection reagents and enzyme substrate molecules in practical training in their second year, which is difficult to do at other schools / departments.
What kind of research are you carrying out?
Fig.3 Purification of a laboriously synthesized reaction product
The most important aim of the graduation work is the preparation of compounds with the desired structure (bioactivity) through organic synthesis. Although high school textbooks note that desired compounds are easily obtained under certain reaction conditions, in fact, in most cases, the preparation is a continual process of trial and error to determine the best conditions. In some cases, unexpected phenomena are observed, leading to the development of a new study subject. This is one of the joys of research. Of course we actively use various reactions to synthesize desired compounds, including the Suzuki-Miyaura coupling developed at our University, and the asymmetric reduction developed by Prof. Noyori. Over the period from just before graduation to entrance into graduate school, students determine the bioactivity of self-synthesized compounds to gain knowledge about the structure-activity relationship. Based on this knowledge, they synthesize new compounds as required and evaluate the expected bioactivity mechanisms, then study the interaction more closely using computer simulations or other techniques. As there are many things that are impossible to do at our laboratory, through joint research with facilities in Japan (Tokyo University, Kyoto University, Osaka University, Suntory Holdings, etc.) and overseas (US, UK), we can comprehensively research a wide range, from the major four components govern the life and homeostasis of living organisms (nucleic acids, proteins, hydrocarbons, and lipids) to bioactive compounds (drugs, pesticides, and poisonous substances).
A message to those who read this booklet
It would be better to think that at universities there are no divisions between biology, physics, and chemistry like at high school. In particular, if you aiming at admission through the general entrance examination, you will have to find your own path from among the various schools and departments after entering university. And once in a department, you must then choose a laboratory. I entered university with having done almost no biology study at high school, and now am focusing on biomolecules (biology). Once the actual study is started, the barriers associated with your background will be easily broken through. So I do not recommend you build walls around yourself in school life.
(1) Review of recent research progress written in English
Recent Progress in Diazirine-Based Photoaffinity Labeling, Eur. J. Org. Chem., 2513-2523 (2008)
(PDF available if requested by email. E-mail: email@example.com)