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...

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Autores principales:	Shahir S. Rizk, Somnath Mukherjee, Akiko Koide, Shohei Koide, Anthony A. Kossiakoff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/065572b166404feeb3517918ff5de3c8
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spelling	oai:doaj.org-article:065572b166404feeb3517918ff5de3c82021-12-02T16:06:50ZTargeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody10.1038/s41598-017-00728-12045-2322https://doaj.org/article/065572b166404feeb3517918ff5de3c82017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00728-1https://doaj.org/toc/2045-2322Abstract 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.Shahir S. RizkSomnath MukherjeeAkiko KoideShohei KoideAnthony A. KossiakoffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shahir S. Rizk Somnath Mukherjee Akiko Koide Shohei Koide Anthony A. Kossiakoff Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
description	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.
format	article
author	Shahir S. Rizk Somnath Mukherjee Akiko Koide Shohei Koide Anthony A. Kossiakoff
author_facet	Shahir S. Rizk Somnath Mukherjee Akiko Koide Shohei Koide Anthony A. Kossiakoff
author_sort	Shahir S. Rizk
title	Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
title_short	Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
title_full	Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
title_fullStr	Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
title_full_unstemmed	Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody
title_sort	targeted rescue of cancer-associated idh1 mutant activity using an engineered synthetic antibody
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/065572b166404feeb3517918ff5de3c8
work_keys_str_mv	AT shahirsrizk targetedrescueofcancerassociatedidh1mutantactivityusinganengineeredsyntheticantibody AT somnathmukherjee targetedrescueofcancerassociatedidh1mutantactivityusinganengineeredsyntheticantibody AT akikokoide targetedrescueofcancerassociatedidh1mutantactivityusinganengineeredsyntheticantibody AT shoheikoide targetedrescueofcancerassociatedidh1mutantactivityusinganengineeredsyntheticantibody AT anthonyakossiakoff targetedrescueofcancerassociatedidh1mutantactivityusinganengineeredsyntheticantibody
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Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody

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