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J. Biol. Chem., Vol. 283, Issue 2, 899-907, January 11, 2008

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Catalytic Features and Eradication Ability of Antibody Light-chain UA15-L against Helicobacter pylori^*

Emi Hifumi, Fumiko Morihara^¶, Kenji Hatiuchi, Takuro Okuda, Akira Nishizono^||, and Taizo Uda^**1

From the Research Center for Applied Medical Engineering, Oita University, Dan-noharu 700, Oita-shi, Oita 870-1192, the ^**Department of Applied Biochemistry, Faculty of Engineering, Oita University, Dan-noharu 700, Oita-shi, Oita 870-1192, ^¶Fukuyama Medical Laboratory Co., Fukuyama-city, Hiroshima 720-8510, the ^||Faculty of Medicine, Department of Infectious Diseases, Oita University, Oita 879-5593, and JST-CREST (Japan Science and Technology Corporation), Kawaguchi City 332-0012, Japan

We have successfully developed a catalytic antibody capable of degrading the active site of the urease of Helicobacter pylori and eradicating the bacterial infection in a mouse stomach. This monoclonal antibody UA15 was generated using a designed recombinant protein UreB, which contained the crucial region of the H. pylori urease β-subunit active site, for immunization. The light chain of this antibody (UA15-L) by itself showed a proteolytic activity to substantially degrade both UreB and the intact urease. Oral administration of UA15-L also significantly reduced the number of H. pylori in a mouse stomach. This is the first example of a monoclonal catalytic antibody capable of functioning in vivo, and such an antibody may have a therapeutic utility in the future.

Received for publication, July 11, 2007 , and in revised form, November 6, 2007.

^* This work was supported by the Japan Science and Technology Agency (Creation of Bio-devices and Bio-systems with Chemical and Biological Molecules for Medicinal Use) and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants 13450344 and 16360416). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Appendices S1 and S2.

¹ To whom correspondence should be addressed: Tel./Fax: 81-97-554-7892; E-mail: uda{at}cc.oita-u.ac.jp.

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