Phage Display Identifies Potential Alzheimer's Drugs

"These peptide sequences are potential new tools for the delivery of medication to the amyloid plaques that are found in Alzheimer's disease, or for new diagnostic tests that would allow early identification and treatment of the disease,” explained senior author Dr. Paul T. Martin, assistant professor of neurosciences at the University of California, San Diego.

Phage display is a relatively new technique that can be used to rapidly screen a library of proteins or peptides. The protein or peptides are expressed as a fusion protein with a coat protein of a bacteriophage. The DNA that encodes the virus proteins (and thus also the fusion protein) resides within the protein coat of the virus particle, and the virus therefore provides a physical link between the protein/peptide and the information that encodes it. Vast libraries of peptides can be screened efficiently for binding to a variety of target molecules (antibodies, enzymes, cell-surface receptors) by incubating the phage library with the target. Non-binding phage is washed away, while the remaining phages are amplified. After several rounds of binding under increasing selection pressure, individual clones are characterized by DNA sequencing.

"It is striking that we found only two peptide sequences, and that they were very similar in structure to one another,” said Dr. Martin. "This suggests that if other sequences do exist, they would most likely be variations on the structures we have already identified.”



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