Researchers at Lawrence Berkeley National Laboratory have developed synthetic peptide-coated magnetic beads that can be used to detect the presence of misfolded proteins in blood samples. Misfolded proteins are a factor in a number of diseases, including prion diseases, Alzheimer’s, and Parkinson’s. To date it has been difficult to detect such proteins in patient blood samples, often because they are present in very small quantities and closely resemble their correctly folded cousins. The new beads bind to specific misfolded proteins in blood samples, paving the way for rapid and convenient diagnosis of diseases that involve misfolded proteins.
To date, there has been no convenient or minimally invasive way to test for proteins related to prion diseases. This poses a problem for diagnosis, but also in making sure that donated blood is free from prion contamination.
This group of researchers has developed a new way of testing for misfolded proteins in blood samples. Their technique involves synthetic peptides, called peptoids, that are attached to magnetic beads.
“Our peptoid beads have the ability to detect the misfolded proteins that act as infectious agents, so could have a significant impact in the realm of prion diseases, but we have also shown that they can seek out the large aggregated proteins that are the disease agents in Alzheimer’s and Parkinson’s diseases, among others,” said Ronald Zuckermann, a researcher involved in the project. “Prion diseases are rare, but there are many misfolded protein-based diseases, which affect millions of people, that are also very poorly understood. And like prion diseases, we need a way to diagnose these slow-onset conditions in the years before symptoms arise.”
By coating magnetic beads with peptoids that mimic the misfolded protein being detected, the beads bind to the protein when they are both present in a blood sample. This results in large protein aggregates. “It’s like Velcro. The aggregated misfolded protein has multiple hooks – multiple binding sites – that will attach to the bead, which is like the complementing sheet,” said Michael Connolly, another researcher involved in the study. “But the natural, correctly folded protein only has a single hook, so its binding affinity is much less.”
Once the misfolded proteins have bound to the beads, they can be removed from the blood sample using a magnet, and they can then be analyzed for the presence of the misfolded proteins using an assay. The process is quick and convenient, and could revolutionize the diagnosis and detection of misfolded protein-based diseases.
“On top of potentially detecting asymptomatic disease carriers, the peptoid-bead assay could be optimized to screen blood and blood products in a cheap and fast manner, a capability that will be very important for avoiding accidental transmission in case of a new prion disease outbreak,” said Simone Hornemann, a third researcher involved in the study.
See a video about the technology below:
Via: Berkeley Lab