DESIGN OF SUPER CATALYTIC ANTIBODIES DESTROYING TARGETING VIRUS AND BACTERIUM

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By immunizing ground-state peptides or proteins, we can produce "super catalytic antibodies" possessing serine protease-like characteristics. In this study, we succeeded in preparing "super catalytic antibodies" such as i41-7, i41SL-1-2, Helicobacter pylon urease and chemokine receptor CCRS peptide, and (iii) others.(i)i41-7We prepared six anti-idiotypic monoclonal antibodies (mAbs) against parent 41S-2 mAb whose light chain is a super catalytic antibody (41S-2-L) capable of degrading targeted HIV-1gp41 molecule. The light and heavy chain possess catalytic triad-like structure composed of Ser, His and Asp in their conformations. Both chains of i41-7 mAb could cleave peptide bond of some peptides such as a polypeptide, TP41-1 (TPRGPDRPEGIEEEGGERDRD), as anticipated.(ii)i41SL-1-2A monoclonal antibody (mAb) i4LSL1-2 was obtained by immunizing the peptide of complementarity determining region-1 (CDRL-1: RSSKSLLYSNGNTYLY) of super catalytic antibody light chain, 41S-2-L, capable of emzymati … More cally destroying the gp41 molecule of HIV-1 envelope. The light and heavy chain of i41SL1-2 i41SL1-2 mAb possess catalytic triads in their structures. Both light and heavy chains of i41SL1-2 mAb degraded the antigenic peptide CDRL-1 within 47 and 57 hr, respectively.(iii)Helicobacter pyroni ureaseThe catalytic activities of the light chain of HpU-2,9,and 18 were investigated using the synthetic peptide SVELIDIGGNRRIFGFNALVDR which is the epitope sequence of HpU-2. The light chains could degrade the epitope peptide as showing biphasic reaction profile. Moreover, it destroyed H.pyloni urease but not BSA.(IV)Chemokine receptor CCR5A monoclonal antibody (mAb), ECL2B-2, was obtained by immunizing a peptide possessing a part of a sequence of a chemokine receptor, CCR-5, which is present as a membrane protein on the surface of macrophage and which plays an important role in HIV infection. The light chain of ECL2B-2 mAb degraded the antigenic peptide CCR-5 within about 100 hr. Surprisingly, the light chain had a very high catalytic reaction rate constant (kcat) of 2.23 min^<-1>, which is greater by factors of tens to hundreds than those of natural catalytic antibodies previously obtained. Less