Rongsheng E Wang, Ying Wang, Yuhan Zhang, Chase Gabrelow, Yong Zhang, Victor Chi, Qiangwei Fu, Xiaozhou Luo, Danling Wang, Sean Joseph, Kristen Johnson, Arnab K Chatterjee, Timothy M Wright, Vân T B Nguyen-Tran, John Teijaro, Argyrios N Theofilopoulos, Peter G Schultz, Feng Wang
A variable region fusion strategy was used to generate an immunosuppressive antibody based on a novel "stalk-knob" structural motif in the ultralong complementary-determining region (CDR) of a bovine antibody. The potent Kv1.3 channel inhibitory peptides Moka1-toxin and Vm24-toxin were grafted into different CDRs of the humanized antibodies BVK and Synagis (Syn) using both β-sheet and coiled-coil linkers. Structure-activity relationship efforts led to generation of the fusion protein Syn-Vm24-CDR3L, which demonstrated excellent selectivity and potency against effector human memory T cells (subnanomolar to picomolar EC50 values)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America