skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: STRUCTURE BASED DESIGN OF PROTEIN LIGANDS: A STUDY OF ANTIBODY-LIKE SCAFFOLDS TARGETED AGAINST THE ANTHRAX TOXIN

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.

Authors:
; ;
Publication Date:
Research Org.:
Los Alamos National Lab., NM (US)
Sponsoring Org.:
US Department of Energy (US)
OSTI Identifier:
772829
Report Number(s):
LA-UR-00-6110
TRN: AH200127%%217
DOE Contract Number:  
W-7405-ENG-36
Resource Type:
Conference
Resource Relation:
Conference: Conference title not supplied, Conference location not supplied, Conference dates not supplied; Other Information: PBD: 1 Dec 2000
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; AFFINITY; ANTIBODIES; ANTIGENS; BACILLUS; CHAINS; DESIGN; PROTEINS; TOXINS

Citation Formats

P. SHIFLETT, E. HONG-GELLER, and ET AL. STRUCTURE BASED DESIGN OF PROTEIN LIGANDS: A STUDY OF ANTIBODY-LIKE SCAFFOLDS TARGETED AGAINST THE ANTHRAX TOXIN. United States: N. p., 2000. Web.
P. SHIFLETT, E. HONG-GELLER, & ET AL. STRUCTURE BASED DESIGN OF PROTEIN LIGANDS: A STUDY OF ANTIBODY-LIKE SCAFFOLDS TARGETED AGAINST THE ANTHRAX TOXIN. United States.
P. SHIFLETT, E. HONG-GELLER, and ET AL. Fri . "STRUCTURE BASED DESIGN OF PROTEIN LIGANDS: A STUDY OF ANTIBODY-LIKE SCAFFOLDS TARGETED AGAINST THE ANTHRAX TOXIN". United States. doi:. https://www.osti.gov/servlets/purl/772829.
@article{osti_772829,
title = {STRUCTURE BASED DESIGN OF PROTEIN LIGANDS: A STUDY OF ANTIBODY-LIKE SCAFFOLDS TARGETED AGAINST THE ANTHRAX TOXIN},
author = {P. SHIFLETT and E. HONG-GELLER and ET AL},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Fri Dec 01 00:00:00 EST 2000},
month = {Fri Dec 01 00:00:00 EST 2000}
}

Conference:
Other availability
Please see Document Availability for additional information on obtaining the full-text document. Library patrons may search WorldCat to identify libraries that hold this conference proceeding.

Save / Share: