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

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

Author information

1
Department of Chemistry and Biochemistry, Indiana University South Bend, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana, USA. srizk@iusb.edu.
2
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
3
Perlmutter Cancer Cener, New York University Langone Medical Center, New York, USA.
4
Department of Medicine, New York University School of Medicine, New York, USA.
5
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, USA.

Abstract

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.

PMID:
28373671
PMCID:
PMC5429742
DOI:
10.1038/s41598-017-00728-1
[Indexed for MEDLINE]
Free PMC Article

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