TOP > Research > Department of Systems and Social Informatics > Department of Complex Systems Science > Life-Science Informatics Group > TSUKAMOTO, Masaki

Comprehensive List of Researchers "Information Knowledge"

Department of Complex Systems Science

Life-Science Informatics Group
Dr. of Science
Research Field
Nucleic acid chemistry / Organic synthesis / Organometallic chemistry

Current Research

Chemical Synthesis of Functional Nucleic Acids, and Development of Methodologies Toward It

We are developing methodologies for the synthesis of oligonucleotides and related compounds based on organic synthesis and organometallic chemistry.  In addition we are researching the design and synthesis of functional nucleic acids that would be useful for gene-based diagnosis, gene therapy, as well as elucidation of mechanism for various phenomena in life science.  Below are summaries explaining the research topics we have investigated so far.

Synthesis and biological activity of cyclic bis(3'–5')diadenylic acid (c-di-AMP) and their analogs[1,2]
c-di-AMP was recently identified as a second messenger monitoring DNA integrity during sporulation in the soil bacterium Bacillus subtilis.  Recent studies have revealed that c-di-AMP has various biological activities.  For example, c-di-AMP induces a type I interferon response in Listeria monocytogenes.  In addition, this molecule has adjuvant activities.  To investigate the unknown biological activities of c-di-AMP, a sufficient amount of this molecule is necessary.  We established a facile synthesis of c-di-AMP and its 2'-modified analogs by a combination of the phosphoramidite and phosphotriester methods.  Investigation of the biological activities of c-di-AMP and its analogs is currently in progress.

(2) Carboxylic acids as promoters for internucleotide-bond formation via condensation of a nucleoside phosphoramidite and a nucleoside
In nucleotide synthesis conducted via the phosphoramidite method, one of the most important issues has been the invention of a useful promoter for condensing a nucleoside phosphoramidite and a nucleoside, forming an internucleotidic phosphityl linkage.  As a promoter, 1H-tetrazole is widely employed at present.  However, this reagent is expensive, explosive, and toxic, thus it is not suitable for large-scale synthesis.  In addition, the reactivity of 1H-tetrazole is not sufficiently high, especially in coupling reactions employing the less reactive phosphoramidite (most of the building blocks for functional nucleic acids are less reactive).  Therefore, development of promoters, which overcome this drawback, would be highly desirable.  We investigated the series of carboxylic acids as promoters, with the investigation revealing that the acid, the pKa value of which in acetonitrile is less than 16, is capable of promoting the condensation reaction.  In carboxylic acids serving as promoters, those with higher acidity generally show greater activity.  In particular, trichloroacetic acid displays high levels of activity and can be used as a promoter for solid-phase synthesis of DNA oligomers.  Because trichloroacetic acid is commercially available at a low price, it has a great advantage over the existent promoters such as 1H-tetrazole and benzimidazolium triflate.  Application of the present method to the synthesis of oligonucleotides and related compounds holds great potential.


  • Masaki Tsukamoto received his Dr. of Science degree from Nagoya University in 1999.
  • He then moved to the Research Center for Materials Science at Nagoya University as a JSPS research fellow.
  • In 2001, he worked as a postdoctoral fellow at the Université Paris-Sud, Orsay.
  • Since 2003, he has been a Research Associate of Graduate School of Information Science, Nagoya University.

Academic Societies

  • The Chemical Society of Japan
  • The Society of Synthetic Organic Chemistry, Japan
  • The American Chemical Society


  1. Synthesis of 2'-Modified Cyclic Bis(3'–5')diadenylic Acids (c-di-AMPs) and Their Promotion of Cell Division in a Freshwater Green Alga. T. Tezuka, N. Suzuki, K. Ishida, K.-i. Oyama, S. Aoki, and M. Tsukamoto, Chem. Lett., 41, 1723–1725 (2012).
  2. Practical Synthesis of Cyclic Bis(3'-5') diadenylic Acid (c-di-AMP). N. Suzuki, K.-i. Oyama, and M. Tsukamoto, Chem. Lett., 40, 1113–1114 (2011).
  3. Carboxylic Acids as Promoters for Internucleotide-Bond Formation via Condensation of a Nucleoside Phosphoramidite and a Nucleoside: Relationship between the Acidity and the Activity of the Promoter. Y. Hayakawa, T. Iwase, E. J. Nurminen, M. Tsukamoto, and M. Kataoka, Tetrahedron, 61, 2203–2209 (2005).