機能性分子化学研究室
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Research Title

Chemical reactions and information-transmissions in living matter are based on recognition of molecules by molecules. We are solving many analytical and biomedical problems of molecular interactions on the basis of analytical chemistry, physical chemistry, organic chemistry, biochemistry and enzymology.

1. Studies on Molecular Recognition of Peptides and Their New Sequence Analysis

It is great important to develop an analytical protocol that permits facile and sensitive determination of various peptides to find new bioactive peptides in mammalian bodies, foods and other natural resources. We have been studying on new chemical reactions with fluorogenic or chemiluminogenic reagents that can be utilized for liquid chromatography (LC). In order to increase sensitivity as well as selectivity, we have developed the optical detection methods selective for Tyr-containing peptides, Arg-containing peptides, N-terminal Try-containing peptides, N-terminal Trp-containing peptides, and recently general peptides. we have studied also newly sequential protocols for proteins, by means of the synthesis of fluorogenic or chemiluminogenic Edman-type reagents.

2. Studies on Super-Sensitive Optical Detection of Nucleic Acids and Proteins

Non-radiochemical methods utilizing fluorescence (FL) or chemiluminescence (CL) reagents for detecting DNA probes or primers are very desirable. They allow the development of powerful analytical techniques for obtaining information on gene structure and function. Recently we found that phenylglyoxal and 3, 4, 5 -trimethoxyphenylglyoxal in situ react with guanine nucleotides to emit CL in a weakly alkaline solution, via a high-energy, 1,2-dioxetane intermediate. This method has been successfully applied in the quantitative detection of nucleic acids and deoxy-guanylic acid oligomers on a solid -phase membrane.
Other research our project is the screening of many CL reactions and to find another new and simple CL-reaction conditions for applying to many fields of immunoassay, DNA hybridization, environmental monitoring and postcolumn chromatographic detection, etc. Now we found a new CL reaction between a basic aqueous hydrogen peroxide and nitrile compounds. Our current data have shown that it is very easy to couple this new reaction to CL imaging for the detection of proteins or nucleic acids on the microplate and membrane with a charge-coupled device camera. Currently, we are attaching many chemiluminogenic molecules into polymer backbone to further increase the sensitivity.

3. Functional analyses of transcription factor and applied research

It is estimated that the human chromosome includes 20,000-30,000 kinds of genes coding proteins by the human genome project. Transcription factors are one of the most important molecules in the vital activity, because they control the transcription of the genes. Functional analyses of the transcription factors are important in not only the understanding of the life phenomenon, but also the treatment of disease and the medicine development.
We research the functional analysis of the transcription factor, which controls the transcription of metabolic enzyme genes. We focus the interactions between the transcription factor and DNA, and between the proteins. And we develop the DNA- and RNA-aptamers, which can specifically bind to target proteins, for the diagnosis and treatment of diseases.

4. Studies on the Development of Novel Functional Nucleic Acids

In recent years, RNA interference (RNAi) - a Nobel Prize-winning research in 2006 - has attracted attention as an effective chemotherapy for diseases caused by genetic disorder. RNAi is an intrinsic system to regulate gene expression in cells, and is a phenomenon in which the expression of a certain protein is suppressed by short double-strand RNA. Therefore, RNAi has a potential for inhibition of disease-causing proteins without inhibiting the functions of normal proteins. At present, researches to apply RNAi for therapy have been conducted all over the world. However, there are only few examples of RNAi method utilized clinically. Our research interest is to develop novel artificial nucleoside(s) and to improve the existing RNAi method, which allows the clinical application of RNAi for diseases caused by genetic disorder.

5. Instruments in Lab

CCD Detector for Fluorescence
and Chemiluminescence
CCD Detector for
Chemiluminescence
Microscope for FL and CL
HPLC system HPLC Protein Sequencer
Fluorophotometer ESI-MS APCI-MS
Incubator Cerculator for PCR Clean Bench
Chemiluminometer Spectrophotometer Lyophilizer