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Combining intracellular selection with protein-fragment complementation to derive A? interacting peptides

Acerra, Nicola, Kad, Neil M, Mason, Jody M (2013) Combining intracellular selection with protein-fragment complementation to derive A? interacting peptides. Protein engineering, design & selection : PEDS, 26 (7). pp. 463-470. ISSN 1741-0126. E-ISSN 1741-0134. (doi:10.1093/protein/gzt021) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1093/protein/gzt021

Abstract

Aggregation of the ?-amyloid (A?) peptide into toxic oligomers is considered the primary event in the pathogenesis of Alzheimer's disease. Previously generated peptides and mimetics designed to bind to amyloid fibrils have encountered problems in solubility, protease susceptibility and the population of small soluble toxic oligomers. We present a new method that opens the possibility of deriving new amyloid inhibitors. The intracellular protein-fragment complementation assay (PCA) approach uses a semi-rational design approach to generate peptides capable of binding to A?. Peptide libraries are based on A? regions responsible for instigating amyloidosis, with screening and selection occurring entirely inside Escherichia coli. Successfully selected peptides must therefore bind A? and recombine an essential enzyme while permitting bacterial cell survival. No assumptions are made regarding the mechanism of action for selected binders. Biophysical characterisation demonstrates that binding induces a noticeable reduction in amyloid. Therefore, this amyloid-PCA approach may offer a new pathway for the design of effective inhibitors against the formation of amyloid in general.

Item Type: Article
DOI/Identification number: 10.1093/protein/gzt021
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: N. Kad
Date Deposited: 15 Sep 2014 19:15 UTC
Last Modified: 29 May 2019 13:05 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/42941 (The current URI for this page, for reference purposes)
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