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

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.

SUBMITTER: Rizk SS

PROVIDER: S-EPMC5429742 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Rizk Shahir S SS Mukherjee Somnath S Koide Akiko A Koide Shohei S Kossiakoff Anthony A AA

Scientific reports 20170403 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. ...[more]

PMID: 28373671

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