研究者業績

臼杵 豊展

ウスキ トヨノブ  (Usuki Toyonobu)

基本情報

所属
上智大学 理工学部物質生命理工学科 教授
学位
学士(理学)(東北大学)
修士(理学)(東北大学)
博士(理学)(東北大学)

連絡先
t-usukisophia.ac.jp
研究者番号
50514535
J-GLOBAL ID
200901076489387829
researchmap会員ID
5000046104

学歴

 3

論文

 113
  • Ayano Tanaka, Yasuhiro Arai, Su-Nam Kim, Jungyeob Ham, Toyonobu Usuki
    JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 13(4) 290-296 2011年  査読有り責任著者
    Concise total synthesis of bilobol 5-pentadecenylresorcinol (1), isolated from Gingko biloba fruits, has been achieved in 10 steps with 51% overall yield from 3,5-dihydroxybenzoic acid (3). Adipostatin A (2), isolated from the fruits as well as from Streptomyces cyaneus 2299-SV1, has also been synthesized in two steps from methylated bilobol (10). The structure-activity relationship study of synthetic products was described by means of cytotoxic assay against human KB carcinoma cell lines.
  • Toyonobu Usuki, Nanae Yasuda, Masahiro Yoshizawa-Fujita, Masahiro Rikukawa
    CHEMICAL COMMUNICATIONS 47(38) 10560-10562 2011年  査読有り筆頭著者責任著者
    Shikimic acid, the starting material in the commercial synthesis of oseltamivir phosphate (Tamiflu (R)), was efficiently extracted and isolated from Ginkgo biloba leaves utilizing the ionic liquid 1-butyl-3-methylimidazolium chloride ([bmim]Cl), which dissolves cellulose.
  • 鈴木江津子, 佐藤麻希子, 臼杵豊展, 岡田隆
    動物心理学研究 60(2) 173 2010年12月25日  
  • Yohei Koseki, Hiroto Yanuma, Takahiro Hayashi, Haruka Yamada, Yong Y. Lin, Toyonobu Usuki
    PEPTIDE SCIENCE -SYMPOSIUM (47) 195 2010年3月  査読有り責任著者
  • Toyonobu Usuki, Mari Kawai, Koji Nakanishi, George A. Ellestad
    Chemical Communications 46(5) 737-739 2010年  査読有り筆頭著者
  • Masayuki Inoue, Nayoung Lee, Keisuke Miyazaki, Toyonobu Usuki, Shigeru Matsuoka, Masahiro Hirama
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47(45) 8611-8614 2008年  査読有り
  • Masahiro Hirama, Kimio Akiyama, Parthasarathi Das, Takashi Mita, Martin J. Lear, Kyo-ichiro Iida, Itaru Sato, Furnihiko Yoshimura, Toyonobu Usuki, Shozo Tero-Kubota
    HETEROCYCLES 69(1) 83-+ 2006年12月  査読有り
    The ESR spectra for synthetic bicyclo[7.3.0]epoxydodecadienediynes in solution at room temperature are steady. These spectra originate from the Masamune-Bergman cyclization of bicyclo[7.3.0]epoxydodecadienediynes to p-benzyne biradicals and the equilibrium between the two forms. Comparison of the ESR spectra of the unlabeled and C-13-labeled nine-membered enediynes indicated that the spectra are not directly due to the p-benzyne biradicals but rather to more stable secondary radical intermediates.
  • Toyonobu Usuki, Koji Nakanishi, George A. Ellestad
    ORGANIC LETTERS 8(24) 5461-5463 2006年11月  査読有り筆頭著者責任著者
    In the presence of thiols, the ten-membered-ring enediyne calicheamicin gamma(l)(1) generates a p-benzyne biradical that initiates oxidative cleavage of double-stranded DNA. Application of spin-trapping has successfully provided ESR and mass spectroscopic evidence for the formation of the monoadducts with phenyl tert-butyl nitrone (PBN).
  • Masayuki Inoue, Toyonobu Usuki, Nayoung Lee, Masahiro Hirama, Toshiyuki Tanaka, Fumihito Hosoi, Shinji Ohie, Toshio Otani
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128(24) 7896-7903 2006年6月  査読有り
    C-1027 is an extremely potent antitumor agent that causes double-stranded DNA cleavages. It is a unique small molecule-protein complex composed of a highly reactive enediyne chromophore, which upon binding reacts with its target molecule DNA through radical-mediated hydrogen abstraction and an apoprotein that encapsulates the chromophore serving as its carrier to reach DNA. Although C-1027 has favorable properties as an effective drug delivery system, it slowly self-decomposes due to the reactivity of the chromophore toward the apoprotein. Understanding how the C-1027 destroys itself may enable design of its analogues that overcome this limitation. In this paper, mechanistic insights into the self-reactivity of C-1027 that facilitates its own decomposition are described. We provide evidence that the formation of the Gly96 radical, which promotes the oxidative protein scission and the subsequent chromophore release, is the major pathway for the self-decomposition of C-1027. On the basis of the newly isolated products of the self-decomposition, we propose that the apoprotein effectively protects two different structural elements of the chromophore that are essential for its biological activity: the nine-membered enediyne moiety (necessary for DNA cleavage) and the benzoxazine moiety (necessary for DNA intercalation). Using an engineered apoprotein analogue kinetically more stable toward the chromophore radical, we show that enhanced overall properties can be achieved for the natural C-1027 with respect to stability and antitumor activities. The results present the first example of a rationally designed C-1027 analogue reported to display superior in vitro antitumor activity to the natural C-1027. Our findings may have implications for design of proteins that can stably encapsulate highly reactive small molecules.
  • Toyonobu Usuki, M Inoue, K Akiyama, M Hirama
    BIOORGANIC & MEDICINAL CHEMISTRY 13(17) 5218-5224 2005年9月  査読有り招待有り筆頭著者
    C-1027 belongs to the family of chromoprotein antitumor antibiotics, which contain a carrier apoprotein and a highly unstable enediyne chromophore. The enediyne spontaneously aromatizes to generate p-benzyne biradical, and subsequently abstracts hydrogens from the DNA sugar backbone, resulting in cleavage of the double strand. Using spin-trapping methods, we obtained direct proof of radical intermediates during an DNA cleavage, and found intriguing difference in behavior between the trapping agents 2-methyl-2-nitrosopropane (MNP) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO): MNP added to the sugar radicals of the DNA, whereas DMPO directly trapped a phenyl radical or p-benzyne biradical derived from the C-1027 chromophore. (c) 2005 Elsevier Ltd. All rights reserved.
  • Toyonobu Usuki, M Inoue, M Hirama, T Tanaka
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126(10) 3022-3023 2004年3月  査読有り筆頭著者
  • Toyonobu Usuki, T Mita, MJ Lear, P Das, F Yoshimura, M Inoue, M Hirama, K Akiyama, S Tero-Kubota
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43(39) 5249-5253 2004年  査読有り筆頭著者
  • Toyonobu Usuki, Masayuki Inoue, Kimio Akiyama, Masahiro Hirama
    CHEMISTRY LETTERS 31(11) 1148-1149 2002年11月  査読有り筆頭著者
    We report the direct observation of radical intermediates in the course of the DNA cleavage induced by the chromoprotein antitumor agent C-1027 using spin-trapping methods. An intriguing difference of behaviors was found between MNP (2-methyl-2-nitrosopropane) and DMPO (5,5-dimethyl-1-pyrroline N-oxide).

MISC

 2

書籍等出版物

 2

講演・口頭発表等

 281

共同研究・競争的資金等の研究課題

 22

その他

 7