Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody

Sci Rep. 2017 Apr 3;7(1):556. doi: 10.1038/s41598-017-00728-1.


We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with brain tumors. The results show that this strategy is a first step towards developing "activator drugs" for a large number of genetic disorders where mutations have disrupted protein function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Catalysis / drug effects
  • Cell Surface Display Techniques
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Isocitrate Dehydrogenase / antagonists & inhibitors*
  • Isocitrate Dehydrogenase / chemistry
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Kinetics
  • Mutation*
  • Peptide Library
  • Thermodynamics


  • Antibodies, Monoclonal
  • Enzyme Inhibitors
  • Peptide Library
  • Isocitrate Dehydrogenase