Member

Research Theme

1. Development of bio-probes, bio-sensing, medicinal chemistry towards chemical biology.
   Bio-probes that specifically recognize each receptor or enzyme are being developed for research on chemical biology involving imaging and sensing. Drug discovery for the chemotherapy of cancer, AIDS, Alzheimer's disease, rheumatoid arthritis, SARS, etc. is being performed based on targeting several receptors, enzymes, etc.
2. Development of conformational-constrained templates for drug discovery.
   Drug-discovery templates for conformational restriction, which enable pharmacophores of bioactive compounds (ex. peptides) to be suitably disposed in three-dimensional space, are being developed.
3. Structural analysis of the interactions between nuclear receptors and the ligands.
   Using X-ray crystal structural analysis, the mechanism of the communication operated by binding of ligands to nuclear receptors is being analyzed.
4. Development of PPAR ligands.
   To discover anti-diabetic agents without side effects, we design and synthesize agonists and antagonists based on the crystal structure of PPAR .

Publications

1. Niida A, Wang Z, Tomita K, Oishi S, Tamamura H, Otaka A, Navenot J-M, Broach JR, Peiper SC, Fujii N: Design and synthesis of downsized metastin (45-54) analogs with maintenance of high GPR54 agonistic activity. Bioor. Med Che. Lett 16(1): 134-137, 2006.
2. Oishi S, Miyamoto K, Niida A, Yamamoto M, Ajito K, Tamamura H, Otaka A, Kuroda Y, Asai A, Fujii N: Application of tri- and tetrasubstituted alkene dipeptide mimetics to conformational studies of cyclic RGD peptides. Tetrahedron 62: 1416-1424, 2006.
3. Kasyanov A, Tamamura H, Fujii N, Xiong H: HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus. Eur J Neuroscience 23: 1120-1128, 2006.
4. Hanaoka H, Mukai T, Tamamura H, Mori T, Ishino S, Ogawa K, Iida Y, Doi R, Fujii N, Saji H: A radiolabeled CXCR4 inhibitor for tumor imaging. Nuc. Med Bio. 33(4): 489-494, 2006.
5. Menu E, Asosingh K, Indraccolo S, De Raeve H, Van Riet I, Van Valckenborgh E, Broek IV, Fujii N, Tamamura H, Van Camp B, Vanderkerken K: The involvement of stromal derived factor 1 in homing and progression of multiple myeloma in the 5TMM model. Haematologica/the Hematology Journal 91(5): 605-612, 2006.
6. Tamamura H, Ojida A, Ogawa T, Tsutsumi H, Masuno H, Nakashima H, Yamamoto N, Hamachi I, Fujii N: Identification of a new class of low molecular weight antagonists against the chemokine receptor CXCR4 having the dipicolylamine-zinc(ii) complex structure. J Med Chem 49(11): 3412-3415, 2006.
7. Tamamura H, Tsutsumi H, Masuno H, Mizokami S, Hiramatsu K, Wang Z, Trent JO, Nakashima H, Yamamoto N, Peiper SC, Fujii N: Development of a linear type of low molecular weight CXCR4 antagonists based on T140 analogs. Org Biomol Chem 4: 2354-2357, 2006.
8. Niida A, Tanigaki H, Inokuchi E, Sasaki Y, Oishi S, Ohno H, Tamamura H, Wang Z, Peiper SC, Kitaura K, Otaka A, Fujii N: Stereoselective synthesis of 3,6-disubstituted-3,6-dihydropyridin-2-ones as potential diketopiperazine mimetics using organocopper-mediated anti-S(N)2 ' reactions and their use in the preparation of low-molecule CXCR4 antagonists. J Org Chem 71(10): 3942-3951, 2006.
9. Ueda S, Oishi S, Wang Z, Araki T, Tamamura H, Cluzeau J, Ohno H, Kusano S, Nakashima H, Trent JO, Peiper SC, Fujii N: Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: Disclosing the importance of side-chain and backbone functionalities. J Med Chem in press.
10. Itoh T, Murota I, Yoshikai K, Yamada S, Yamamoto K. Synthesis of docosahexaenoic acid derivatives designed as novel PPAR agonists and antidiabetic agents. Bioorg Med Chem. 14, 98-108: 2006.
11. Shimizu M, Iwasaki Y, Kobayashi E, Shimazaki M, Yamamoto K, Wolfgang R, Yamada S. Synthesis and Biological Activities of New 1 ,25-Dihydroxy-19-norvitamin D3 Analogs with Modification in Both the A-Ring and the Side Chain. Bioorg. Med. Chem.14: 4277-4294, 2006.
12. Yamamoto K, Abe D, Yoshimoto N, Choi M, Yamagishi K, Tokiwa H, Shimizu M, Makishima M, Yamada S. Vitamin D Receptor: Ligand Recognition and Allosteric Network. J. Med. Chem. 49: 1313-1324, 2006.
13. Yamagishi K, Yamamoto K, Yamada S, Tokiwa H. Functions of Key Residues in the Ligand-Binding Pocket of Vitamin D Receptor: Fragment Molecular Orbital-Interfragment Interaction Energy Analysis. Chem. Phys. Lett. 420: 465-468, 2006.
14. Shimazaki M, Miyamoto Y, Yamamoto K, Yamada S, Takami M, Shinki T, Udagawa N, Shimizu M. Analogs of 1 ,25-dihydroxyvitamin D3 with high potency in induction of osteoclastogenesis and prmapion of dendritic cell differentiation: Synthesis and biological evaluation of 2-substituted 19-norvitamin D analogs. Bioorg Med Chem. 14: 4645-4656, 2006.
15. Urushino N, Yamamoto K, Kagawa K, Ikushiro S, Kamakura M, Yamada S, Kato S, K Inouye K, Sakaki｡｡T. Interaction between mitochondrial CYP27B1 and adrenodoxin: Role of arg458 of mouse CYP27B1. Biochemistry. 45: 4405-4412, 2006.
16. Hamamoto H, Kusudo T, Masuno H, Yamamoto K, Yamada S, Kamakura M, Ohta M, Inouye K, Sakaki T. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: Amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol. Pharmcol. 70: 120-128, 2006.
17. Aiba I, Yamasaki T, Shinki T, Izumi S, Yamamoto K, Yamada S, Terato H, Ide H, Ohyama Y. Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroid. 71: 849-856, 2006.
18. Akio Ojida, Masa-aki Inoue, Yasuko Mito-oka, Hiroshi Tsutsumi, Kazuki Sada, Itaru Hamachi: Effective Disruption of Phosphoprotein-Protein Surface Interaction Using Zn(II) Dipicolylamine-Based Artificial Receptors via Two-Point Interaction, J Am Chem Soc 128: 2052-2058, 2006.
19. Yousuke Takaoka, Hiroshi Tsutsumi, Noriyuki Kasagi, Eiji Nakata, and Itaru Hamachi: One-pot and Sequential Organic Chemistry on an Enzyme Surface to Tether a Fluorescent Probe at the Proximity of the Active Site with Restoring Enzyme Activity, J Am Chem Soc 128: 3273-3280, 2006.