Synthetic Inhibitors of Proteins

We aimed to develop “dual functional” inhibitors targeted against influenza hemagglutinin and sialidase. Our dream is to reduce the emergence of drug-resistant strains.

1. Sun, X.-L. et al. Eur. J. Org. Chem., 2000, 14, 2643-2653.
   

2. Guo, C.-T. et al. Glycobiology, 2002, 12, 183-190.
   

Inhibitors of glycosidases: azasugars and carbasugars

                                                    

Five membered azasugars are potent inhibitors of glycosidases. The type of compound is considered to mimic a transition state. We started the project at RIKEN institute with Prof. Chi-Huey Wong. Up until now, we fond very strong and specific inhibitors against GlcNAc-ase and GalNAc-ase, respectively.

1. Takebayashi, M. et al. J. Org. Chem., 1999, 64, 5280-5291.
   

2. Saotome, C. et al. Bioorg. Med. Chem., 2000, 8, 2249-2261.
   

3. Saotome, C. et al. Chem. Biol., 2001, 8, 1061-1070.
   

4. Nakahara, T. et al. Carbohydr. Res., 2008, 343, 1624-1635.
   

GM3 containing polymer (polyglutamate) was found to be extremely potent inhibitor of influenza infection. The substitution content of the ligand glycan is surprisingly ca 1%.

1. Kamitakahara, H. et al. Angew. Chem. Int. Ed., 1998, 37, 1524-1528.
   

Alpha-Galactosyl Ceramide

Synthesis and evaluation of analogues of alpha-Gal-Cer

Collaboration with Dr. Shimamura. We discovered alpha-Man-Cer specifically induced a NKT cell repertoire.

1. Shimamura, M. et al. Eur J Immunol, 2004, 34, 735-742.
   

2. Okamoto, N. et al. Chem. Biol. 2005, 12, 677-683.
   

Synthetic methodology in oligosaccharide synthesis

1. Kanie, O. et al. J. Am. Chem. Soc., 1994, 116, 12073-12074.
   

2. Kanie, O. et al Tetrahedron Lett., 1996, 37, 4551-4554.
   

3. Ito, Y. et al. Angew. Chem. Int. Ed., 1996, 35, 2510-2512.
   

A new catalyst for the hydrogenation! A stable nanoparticle of Palldium(0) is very much stronger catalyst than ordinary Pd/C, and it works for solid-phase synthesis.

We confirmed this particle is stable for more than 10 years as a solution.

1. Kanie, O. et al. Angew. Chem. Int. Ed., 2000, 39, 4545-4547.
   

Monitoring of solid-phase reactions by 13C NMR

A non-destructive method of quantitative monitoring of solid-phase synthesis. A set of stable isotopes were used to monitor the reaction course where one is used as "a stationary beacon".

1. Kanemitsu, T. et al. Angew. Chem. Int. Ed., 1998, 38, 3415-3418.
   

2. Kanemitsu, T. et al. J. Am. Chem. Soc, 2002, 124, 3591-3599.
   

3. Kanemitsu, T. et al. J. Carbohydr. Chem., 2006, 25, 361-376.
   

A most challenging chemistry, synthesis of a combinatoial oligosaccharide library.

1. Suzuki, K. et al. J. Carbohydr. Chem, 2005, 24, 219-236.
   

2. Kanie, O. et al. Angew. Chem. Int. Ed., 2006, 45, 3851-3854.
   

3. Ohtsuka, I. et al. Carbohydr. Res., 2006, 341, 1476-1487
   

4. Ako, T. et al. Chem. Asian J., 2006, 1, 798-813.
   

Illustration by Shin