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Structure based design of protein ligands: a study of antibody-like scaffolds targeted against the anthrax toxin.

DE2001772829

Publication Date	2000
Personal Author	Shiflett, P.; Hong-Geller, E.
Page Count	5
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 V(sub L) on the N terminus and V(sub H) on the C-terminus and joined them by a 10 amino-acid-long linker. This scaffold preserves the native V(sub L)-V(sub H) 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.
Keywords	Affinity Antibodies Antigens Bacillus Chains Design Proteins Toxins
Source Agency	Technical Information Center Oak Ridge Tennessee
NTIS Subject Category	57F - Cytology, Genetics, & Molecular Biology
Corporate Authors	Los Alamos National Lab., NM.; Department of Energy, Washington, DC.
Document Type	Conference Proceedings
NTIS Issue Number	200125
Contract Number	W-7405-ENG-36

Structure based design of protein ligands: a study of antibody-like scaffolds targeted against the anthrax toxin.

Structure based design of protein ligands: a study of antibody-like scaffolds targeted against the anthrax toxin.
DE2001772829

Publication Date	2000
Personal Author	Shiflett, P.; Hong-Geller, E.
Page Count	5
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 V(sub L) on the N terminus and V(sub H) on the C-terminus and joined them by a 10 amino-acid-long linker. This scaffold preserves the native V(sub L)-V(sub H) 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.
Keywords	Affinity Antibodies Antigens Bacillus Chains Design Proteins Toxins
Source Agency	Technical Information Center Oak Ridge Tennessee
NTIS Subject Category	57F - Cytology, Genetics, & Molecular Biology
Corporate Authors	Los Alamos National Lab., NM.; Department of Energy, Washington, DC.
Document Type	Conference Proceedings
NTIS Issue Number	200125
Contract Number	W-7405-ENG-36