Nano Science and Technology Institute
Nanotech 2001 Vol. 2
Nanotech 2001 Vol. 2
Technical Proceedings of the 2001 International Conference on Computational Nanoscience and Nanotechnology
 
Chapter 1: Computational Biology and Molecular Design
 

Structure Based Design of Protein Ligands: A Study of Antibody-like Scaffolds Targeted Against the Anthrax Toxin

Authors:P. Shiflett, E. Hong-Geller, D. Allen, S. Lauer, N. Lehnert, J. Nolan, B. Lehnert and G. Gupta
Affilation:Los Alamos National Laboratories, US
Pages:25 - 28
Keywords:structure based, design, proteins, antibody, scaffolds, anthrax
Abstract:We have adopted structure-based approaches to enhance the affinities of two single chain antibodies, scFv1 and scFv4, that bind to two different epitopes on the Protective Antigen (PA), a toxin from Bacillus anthracis. In one approach, we have modified scFv4 and re-engineered a novel antibody-like scaffold in which we have placed VL on the N terminus and VH on the C-terminus and joined them by a 10 amino-acid-long linker. This scaffold preserves the native VL-VH contact interface and the dispositions of the CDR loops. It binds to PA with 10 fold higher affinity than scFv4. In a second approach, we have created a bispecific ligand by covalently joining scFv1 and scFv4 by a flexible linker that supports simultaneous and synergistic binding of the two scFvs to PA. This bispecific scFv1-linker-scFv4 binds to PA with 10 fold higher affinity than the individual scFvs. The newly re-engineered antibody-like scaffold of scFv4 and scFv1-linker-scFv4 are expected to be potent inhibitors of PA binding to the host cells.
Structure Based Design of Protein Ligands: A Study of Antibody-like Scaffolds Targeted Against the Anthrax ToxinView PDF of paper
ISBN:0-9708275-3-9
Pages:218
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