TY - JOUR
T1 - Antibody Clicking as a Strategy to Modify Antibody Functionalities on the Surface of Targeted Cells
AU - Komatsu, Toru
AU - Kyo, Etsu
AU - Ishii, Haruki
AU - Tsuchikama, Kyoji
AU - Yamaguchi, Aiko
AU - Ueno, Tasuku
AU - Hanaoka, Kenjiro
AU - Urano, Yasuteru
N1 - Funding Information:
Financial support for this study was provided by MEXT (24655147, 15H05371, 15K14937, 17K19477, 18H04538, 19H02846, and 20H04694 to T.K.), JST (PRESTO, PRESTO Network, and CREST to T.K.), AMED (CREST to Y.U.), and the DoD (W81XWH-18-1-0004 and W81XWH-19-1-0598 to K.T.). The project was also supported by JSPS Core-to-Core program (JPJSCCA20170007). T.K. was supported by The Naito Foundation, The Mochida Memorial Foundation for Medical and Pharmaceutical Research, and The Tokyo Biochemical Research Foundation.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/9/16
Y1 - 2020/9/16
N2 - We established a methodology for initiating cross-linking of antibodies selectively on the cell surface through intermolecular copper-free click reactions facilitated by increased effective concentrations of antibodies binding to target antigens. Upon cross-linking of tetrazine- and bicyclononyne-modified trastuzumab on the surface of HER2-overexpressing cells, increased antibody uptake and activation of intracellular signaling were observed. Our findings demonstrate that the cross-linking reaction can significantly alter the biophysical properties of proteins, activating their unique functionalities on targeted cells to realize an increased cargo delivery and synthetic manipulation of cellular signaling.
AB - We established a methodology for initiating cross-linking of antibodies selectively on the cell surface through intermolecular copper-free click reactions facilitated by increased effective concentrations of antibodies binding to target antigens. Upon cross-linking of tetrazine- and bicyclononyne-modified trastuzumab on the surface of HER2-overexpressing cells, increased antibody uptake and activation of intracellular signaling were observed. Our findings demonstrate that the cross-linking reaction can significantly alter the biophysical properties of proteins, activating their unique functionalities on targeted cells to realize an increased cargo delivery and synthetic manipulation of cellular signaling.
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U2 - 10.1021/jacs.0c05331
DO - 10.1021/jacs.0c05331
M3 - Article
C2 - 32897068
AN - SCOPUS:85091127178
SN - 0002-7863
VL - 142
SP - 15644
EP - 15648
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 37
ER -