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DNA fragmentation-based combinatorial approaches to soluble protein expression Part I. Generating DNA fragment libraries

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Date
2007-11
ICR Author
Prodromou, Chrisostomos
Author
Prodromou, C
Sawa, R
Driscoll, PC
Type
Journal Article
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Abstract
In addressing a new drug discovery target, the generation of tractable protein substrates for functional and structural analyses can represent a significant hurdle. Traditional approaches rely on protein expression trials of multiple variants in various systems, frequently with limited success. The increasing knowledge base derived from genomics and structural proteomics initiatives assists the bioinformaticsled design of these experiments. Nevertheless, for many eukaryotic polypeptides, particularly those with relatively few homologues, the generation of useful protein products can still be a major challenge. This review describes the basis of efforts to forge an alternative ‘domain-hunting’ paradigm, based upon combinatorial sampling of expression construct libraries derived by fragmentation of the encoding DNA template, namely the methods and considerations in generating fragment length DNA from target genes. An accompanying review focuses upon the expression screening of such combinatorial DNA libraries for the sampling of the corresponding set of protein fragments.
URI
https://repository.icr.ac.uk/handle/internal/2472
DOI
https://doi.org/10.1016/j.drudis.2007.08.012
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  • Other ICR Research
Language
eng
License start date
2007-11
Citation
DRUG DISCOVERY TODAY, 2007, 12 pp. 931 - 938
Publisher
ELSEVIER SCI LTD

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