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Article

Construction of a Humanized Artificial VHH Library Reproducing Structural Features of Camelid VHHs for Therapeutics

1
Epsilon Molecular Engineering, Inc., Saitama 338-8570, Japan
2
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
3
Mitsui Knowledge Industry Co., Ltd., Tokyo 164-0003, Japan
*
Author to whom correspondence should be addressed.
Antibodies 2022, 11(1), 10; https://doi.org/10.3390/antib11010010
Received: 2 December 2021 / Revised: 7 January 2022 / Accepted: 24 January 2022 / Published: 30 January 2022
A variable domain of heavy chain antibody (VHH) has different binding properties than conventional antibodies. Conventional antibodies prefer binding to the convex portion of the antigen, whereas VHHs prefer epitopes, such as crevices and clefts on the antigen. Therefore, developing candidates with the binding characteristics of camelid VHHs is important. Thus, To this end, a synthetic VHH library that reproduces the structural properties of camelid VHHs was constructed. First, the characteristics of VHHs were classified according to the paratope formation based on crystal structure analyses of the complex structures of VHHs and antigens. Then, we classified 330 complementarity-determining region 3 (CDR3) structures of VHHs from the Protein Data Bank (PDB) into three loop structures: Upright, Half-Roll, and Roll. Moreover, these structures depended on the number of amino acid residues within CDR3. Furthermore, in the Upright loops, several amino acid residues in the FR2 are involved in the paratope formation, along with CDR3, suggesting that the FR2 design in the synthetic library is important. A humanized synthetic VHH library, comprising two sub-libraries, Upright and Roll, was constructed and named PharmaLogical. A validation study confirmed that our PharmaLogical library reproduces VHHs with the characteristics of the paratope formation of the camelid VHHs, and shows good performance in VHH screening. View Full-Text
Keywords: variable domain of heavy chain antibodies; synthetic library; cDNA display; therapeutic antibodies; high throughput screening variable domain of heavy chain antibodies; synthetic library; cDNA display; therapeutic antibodies; high throughput screening
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MDPI and ACS Style

Murakami, T.; Kumachi, S.; Matsunaga, Y.; Sato, M.; Wakabayashi-Nakao, K.; Masaki, H.; Yonehara, R.; Motohashi, M.; Nemoto, N.; Tsuchiya, M. Construction of a Humanized Artificial VHH Library Reproducing Structural Features of Camelid VHHs for Therapeutics. Antibodies 2022, 11, 10. https://doi.org/10.3390/antib11010010

AMA Style

Murakami T, Kumachi S, Matsunaga Y, Sato M, Wakabayashi-Nakao K, Masaki H, Yonehara R, Motohashi M, Nemoto N, Tsuchiya M. Construction of a Humanized Artificial VHH Library Reproducing Structural Features of Camelid VHHs for Therapeutics. Antibodies. 2022; 11(1):10. https://doi.org/10.3390/antib11010010

Chicago/Turabian Style

Murakami, Taihei, Shigefumi Kumachi, Yasuhiro Matsunaga, Miwa Sato, Kanako Wakabayashi-Nakao, Hidekazu Masaki, Ryo Yonehara, Maiko Motohashi, Naoto Nemoto, and Masayuki Tsuchiya. 2022. "Construction of a Humanized Artificial VHH Library Reproducing Structural Features of Camelid VHHs for Therapeutics" Antibodies 11, no. 1: 10. https://doi.org/10.3390/antib11010010

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