Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Protein Engineering of Diabodies (#257)

Thomas Weller 1 , Blake Riley 1 , David Hoke 1 , Paul Conroy 2 , Ashley Buckle 1
  1. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Doncaster, Vic, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic, Australia

Diabodies are bivalent and mono or bispecific antibody fragments currently used in diagnostics and as cancer therapeutics.1,2 These fragments have two outward facing binding domains in a back-to-back conformation. Structural analysis suggests that diabodies possess conformational flexibility, which may impact on their function and stability. We are using protein engineering and computational approaches in order to explore diabody dynamics with the aim of modulating their conformational properties and thus potential application.

  1. Weiskopf, K. et al (2016). "CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer." J Clin Invest 126(7): 2610-2620.
  2. Kim, J. H. et al (2016). "Crystal structures of mono- and bi-specific diabodies and reduction of their structural flexibility by introduction of disulfide bridges at the Fv interface." Sci Rep 6: 34515.