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Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting |
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| Authors: | Dong-Sik Kim Jeong-Sun Kim Myung-Hee Kwon |
| Affiliation: | a Department of Molecular Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon 443-749, Republic of Korea b Department of Chemistry, Chonnam National University, 300, Yongbong-dong, Buk-gu, Gwangju 500-757, Republic of Korea c Department of Genetic Engineering, Sungkyunkwan University, 300 Chunchun-dong, Jangan-gu, Suwon 440-746, Republic of Korea d Department of Microbiology, Ajou University School of Medicine, Suwon 442-721, Republic of Korea |
| Abstract: | Humanization of nonhuman antibodies (Abs) has been carried out mainly for Abs which bind to antigen without catalytic activity. Here we report humanization of mouse-originated 3D8 (m3D8) mAbs (scFv, VH, and VL) with DNA hydrolyzing catalytic activity by grafting the complementarity determining regions (CDRs) into the corresponding regions of a fixed human framework scaffold, generating humanized 3D8 (h3D8) Abs in the respective format of scFv, VH, and VL. h3D8 Abs retained comparable DNA binding and hydrolyzing activities to those of the corresponding m3D8 Abs. Our results suggest that CDRs of anti-DNA hydrolyzing Abs might possess the intrinsic properties of DNA binding and hydrolyzing activities. |
| Keywords: | Antibody humanization Anti-DNA hydrolyzing antibody Catalytic antibody CDR grafting Molecular modeling |
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