Next Article in Journal
Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy
Next Article in Special Issue
Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids
Previous Article in Journal
The Flagellar Gene Regulates Biofilm Formation and Mussel Larval Settlement and Metamorphosis
Previous Article in Special Issue
On-Membrane Dynamic Interplay between Anti-GM1 IgG Antibodies and Complement Component C1q
Open AccessArticle

Chemically Crosslinked Bispecific Antibodies for Cancer Therapy: Breaking from the Structural Restrictions of the Genetic Fusion Approach

Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11 Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 711; https://doi.org/10.3390/ijms21030711
Received: 31 October 2019 / Revised: 8 January 2020 / Accepted: 13 January 2020 / Published: 21 January 2020
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
Antibodies are composed of structurally and functionally independent domains that can be used as building blocks to construct different types of chimeric protein-format molecules. However, the generally used genetic fusion and chemical approaches restrict the types of structures that can be formed and do not give an ideal degree of homogeneity. In this study, we combined mutation techniques with chemical conjugation to construct a variety of homogeneous bivalent and bispecific antibodies. First, building modules without lysine residues—which can be chemical conjugation sites—were generated by means of genetic mutation. Specific mutated residues in the lysine-free modules were then re-mutated to lysine residues. Chemical conjugation at the recovered lysine sites enabled the construction of homogeneous bivalent and bispecific antibodies from block modules that could not have been so arranged by genetic fusion approaches. Molecular evolution and bioinformatics techniques assisted in finding viable alternatives to the lysine residues that did not deactivate the block modules. Multiple candidates for re-mutation positions offer a wide variety of possible steric arrangements of block modules, and appropriate linkages between block modules can generate highly bioactive bispecific antibodies. Here, we propose the effectiveness of the lysine-free block module design for site-specific chemical conjugation to form a variety of types of homogeneous chimeric protein-format molecule with a finely tuned structure and function. View Full-Text
Keywords: antibody; bioinformatics; chemical conjugation antibody; bioinformatics; chemical conjugation
Show Figures

Graphical abstract

MDPI and ACS Style

Ueda, A.; Umetsu, M.; Nakanishi, T.; Hashikami, K.; Nakazawa, H.; Hattori, S.; Asano, R.; Kumagai, I. Chemically Crosslinked Bispecific Antibodies for Cancer Therapy: Breaking from the Structural Restrictions of the Genetic Fusion Approach. Int. J. Mol. Sci. 2020, 21, 711. https://doi.org/10.3390/ijms21030711

AMA Style

Ueda A, Umetsu M, Nakanishi T, Hashikami K, Nakazawa H, Hattori S, Asano R, Kumagai I. Chemically Crosslinked Bispecific Antibodies for Cancer Therapy: Breaking from the Structural Restrictions of the Genetic Fusion Approach. International Journal of Molecular Sciences. 2020; 21(3):711. https://doi.org/10.3390/ijms21030711

Chicago/Turabian Style

Ueda, Asami; Umetsu, Mitsuo; Nakanishi, Takeshi; Hashikami, Kentaro; Nakazawa, Hikaru; Hattori, Shuhei; Asano, Ryutaro; Kumagai, Izumi. 2020. "Chemically Crosslinked Bispecific Antibodies for Cancer Therapy: Breaking from the Structural Restrictions of the Genetic Fusion Approach" Int. J. Mol. Sci. 21, no. 3: 711. https://doi.org/10.3390/ijms21030711

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop