The Protein Journal

, 27:292

A Dual-Purpose Protein Ligand for Effective Therapy and Sensitive Diagnosis of Anthrax

  • Momchilo Vuyisich
  • S. Gnanakaran
  • Julie A. Lovchik
  • C. Rick Lyons
  • Goutam Gupta


This article reports the design of a bivalent protein ligand with dual use in therapy and diagnosis of anthrax caused by Bacillus anthracis. The ligand specifically binds to PA and thereby blocks the intracellular delivery of LF and EF toxins that, respectively, cause cell lysis and edema. The ligand is a chimeric scaffold with two PA-binding domains (called VWA) linked to an IgG-Fc frame. Molecular modeling and binding measurements reveal that the VWA-Fc dimer binds to PA with high affinity (KD = 0.2 nM). An in vitro bio-luminescence assay shows that VWA-Fc (at nanomolar concentration) protects mouse macrophages from lysis by PA/LF. In vivo studies demonstrate that VWA-Fc at low doses (∼50  μg/animal) are able to rescue animals from lethal doses of PA/LF and B. anthracis spores. Finally, VWA-Fc is utilized as the capture molecule in the sensitive (down to 30 picomolar) detection of PA using surface plasmon resonance.


Anthrax Lethal toxins Bivalent protein chimera Therapy Detection 



Colony forming units


Capillary morphogenesis protein 2


Edema factor


Flow cell 1




Association rate


Dissociation constant


Lethal factor


Molecular dynamics


Minimum inhibitory concentration


Protective antigen


Response units


Surface plasmon resonance


Tumor endothelial marker 8


Von Willebrand factor A


Bivalent chimeric PA ligand with Fc fusion


VWA domain with C-terminal Histidine tag


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Momchilo Vuyisich
    • 1
  • S. Gnanakaran
    • 2
  • Julie A. Lovchik
    • 3
  • C. Rick Lyons
    • 3
  • Goutam Gupta
    • 1
  1. 1.Biosciences Division, Group B-7Los Alamos National LaboratoryLos AlamosUSA
  2. 2.Theory Division, Group T-10Los Alamos National LaboratoryLos AlamosUSA
  3. 3.Center for Infectious Diseases and Immunity, University of New Mexico Health Science CenterUniversity of New MexicoAlbuquerqueUSA

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