Spectroscopic studies of amyloidic proteins

Proteins are made of small "building blocks", amino acids. Our cells produce twenty different amino acids which can be arranged in different ways to determine the kind of protein that we get.

Moreover, before the protein can start its work it must fold into its functional form. Sometimes this process goes wrong. Incorrectly folded proteins are an important part of the problem for many serious diseases: Alzheimer's, Parkinson's, type II diabetes, Creutzfeldt-Jakob, cancer, cystic fibrosis, and many more.

The Alzheimer's puzzle is actually a whole series of unknown biochemical events. But something links them - this protein that does so much damage on the road to becoming a fibril. What is it that goes wrong, and how can we find new means to study these protein misfolding processes?

Luminescent probes are sensitive to detect hidden species as the probes report back well-defined light upon interrogating with light of another wavelength. There exist many fluorescent probes that bind specifically to protein amyloidic structures, notably, thioflavins (ThT, ThS) and Congo red. These probes dramatically increases their quantum efficiency upon protein binding, however, the emitted spectral distribution is insensitive to the detailed nature of the protein.

Together with Peter Nilsson and Per Hammarström of Linköping University are developing and studying a new type of fluorescent probe that has certain advantages compared with the commonly used ones, so called "Luminescent conjugated polythiophenes" (LCPs). These give in addition to changes of emitted light intensity upon protein binding, different spectral signatures depending on the typa AND conformation of the protein. The image below is a fluorescence microscopy image of protein amyloids stained with such fnew fluorescent probes.

For recent results in an international collaboration project, see a recent publication in ACS Chemical Biology, Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses.

Contact: Mikael Lindgren

Fluorescent probe PTAA developed and exploited togther with Linköping University. Transthyretin is a protein involved in the protein disease: Familial amyloidotic poly-neuropathy).

Laser scanning microscope image of protein amyloids stained with novel LCP fluorescent probes. Image: Mikael Lindgren