Phage display screening for peptides that inhibit polyglutamine aggregation.

Daniel J Kenan; Warren J Strittmatter; James R Burke

doi:10.1016/s0076-6879(06)13014-1

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Phage display screening for peptides that inhibit polyglutamine aggregation.

Daniel J Kenan·Warren J Strittmatter·James R Burke

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Abstract

Proteins with expanded polyglutamine domains cause nine dominantly inherited, neurodegenerative diseases, including Huntington's disease. There are no therapies that inhibit disease onset or progression. To identify a novel therapeutic, we screened phage displayed peptide libraries for phage that bind preferentially to expanded polyglutamine repeats. We identified a peptide motif that inhibits polyglutamine aggregation in vitro and inhibits death in cellular and Drosophila models of the polyglutamine repeat diseases. In this chapter, we describe in detail how to screen a peptide phage display library and highlight results demonstrating the success of this approach. A similar experimental approach could be used for other diseases caused by conformational change in disease proteins, including prion, Alzheimer's, and Parkinson's diseases.

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Amino Acid Sequence Animals Antibodies, Viral Bacteriophage M13 Capsid Proteins DNA-Binding Proteins Drosophila Enzyme-Linked Immunosorbent Assay Heredodegenerative Disorders, Nervous System Humans Peptide Library Peptides Protein Structure, Quaternary Viral Fusion Proteins Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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Daniel J Kenan, Warren J Strittmatter, James R Burke. 2006. Phage display screening for peptides that inhibit polyglutamine aggregation.. https://doi.org/10.1016/s0076-6879(06)13014-1

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