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 -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.
Catalytic antibodies capable of digesting crucial proteins of pathogenic bacteria have long been sought for potential therapeutic use. Helicobacter pylori urease plays a crucial role for the survival of this bacterium in the highly acidic conditions of human stomach. The HpU‐9 monoclonal antibody (mAb) raised against H. pylori urease recognized the α‐subunit of the urease, but only slightly recognized the β‐subunit. However, when isolated both the light and the heavy chains of this antibody were mostly bound to the β‐subunit. The cleavage reaction catalyzed by HpU‐9 light chain (HpU‐9‐L) followed the Michaelis‐Menten equation with a Km of 1.6 × 10−5 m and a kcat of 0.11 min−1, suggesting that the cleavage reaction was enzymatic. In a cleavage test using H. pylori urease, HpU‐9‐L efficiently cleaved the β‐subunit but not the α‐subunit, indicating that the degradation by HpU‐9‐L had a specificity. The cleaved peptide bonds in the β‐subunit were L121‐A122, E124‐G125, S229‐A230, Y241‐D242, and M262‐A263. BSA was hardly cleaved by HpU‐9‐L, again indicating the digestion by HpU‐9‐L was specific. In summary, we succeeded in the preparation of a catalytic antibody light chain capable of specifically digesting the β‐subunit of H. pylori urease.
New Diarylheptanoids from Alnus japonica and Their Antioxidative Activity. -Diarylheptanoids (I) are isolated from the leaves of Alnus japonica. The main constituent is oregonin (Ic). It is shown that compounds having a catechol structure possess antioxidative activities. -(KUROYANAGI*, M.; SHIMOMAE, M.; NAGASHIMA, Y.; MUTO, N.; OKUDA, T.; KAWAHARA, N.; NAKANE, T.; SANO, T.; Chem.
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