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  Targeting intrinsically disordered proteins in rational drug discovery.

Ambadipudi, S., & Zweckstetter, M. (2016). Targeting intrinsically disordered proteins in rational drug discovery. Expert Opinion on Drug Discocery, 11(1), 65-77. doi:10.1517/17460441.2016.1107041.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-7536-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-91B2-4
Genre: Journal Article

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 Creators:
Ambadipudi, S., Author
Zweckstetter, M.1, Author              
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: drug discovery; intrinsically disordered protein; neurodegeneration; NMR spectroscopy
 Abstract: Introduction: Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) have gained wide recognition over the past decade due to their versatile roles in cell physiology and pathology. A large repertoire of IDPs/IDPRs has been implicated in numerous diseases, making them potential targets for therapeutic intervention. Recent advances in experimental methods and computational approaches have enabled detection and characterization of these highly dynamic proteins at atomistic detail, thus facilitating disorder/dynamic-based drug discovery.Areas covered: This article presents an overview of the functional relevance and pathological implications of IDPs/IDPRs in cells. The authors outline the currently available experimental methods employed for structural characterization of these proteins. They also exemplify the practical limitations encountered during such characterization and ways to overcome them. Taken together, the article discusses the plausibility of exploiting protein disorder for drug targeting.Expert opinion: Disorder-based drug targeting is gearing up in the realm of novel drug discovery approaches. Tools for probing the molecular features of IDPs and IDPRs are rapidly improving and start to provide accurate descriptions of the complex ensembles populated by IDPs/IDPRs. They thus pave the way for the development of drug molecules, which specifically target disease-associated disorder.

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Language(s): eng - English
 Dates: 2015-11-072016-01-02
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1517/17460441.2016.1107041
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Title: Expert Opinion on Drug Discocery
Source Genre: Journal
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Pages: - Volume / Issue: 11 (1) Sequence Number: - Start / End Page: 65 - 77 Identifier: -