Optical Reporting by Conjugated Polymers via Conformational Changes - Advanced Fluorescence Reporters in Chemistry and Biology - page 412

classification of protein deposits (Fig. 20 ). These conformation- dependent spectral
characteristics can only be afforded by LCPs and provide the opportunity to opti-
cally fingerprint protein aggregates correlating to distinct prion strains.
The study by Sigurdson et al. also provided evidence that the different spectral
signatures obtained from PTAA were associated with distinct conformations of the
prion aggregates [ 35 ]. Recombinant mouse prion protein (mPrP) was converted into
two different types of amyloid fibrils by using varying conditions for fibrillation. As
these two preparations of fibrils were chemically identical, having the same protein
(mPrP), the spectral differences seen for PTAA was likely due to structural differ-
ences between the fibrils. Hence, the author showed that CPs provide structural
insights regarding the morphology of individual protein deposits and that these
molecular tools could be used as a complementary technique to conventional
staining protocols for the characterization of protein deposits associated with
individual prion strains. These findings might be of great value, as phenomena
similar to those occurring in prion strains may be much more frequent than is now
appreciated, and may extend to additional protein misfolding and aggregation
disorders. As mentioned earlier, strain-like conformational variants can also be
found for A

aggregates, the pathological hallmark of AD. LCPs might therefore
aid in the fundamental understanding of conformational protein variants in a wide
range of protein misfolding disorders.

b

5.3 Novel Molecular Scaffolds for In Vivo Imaging

As shown in the previous sections, CP materials that originate from electronics and
solar cells have proven very useful as a novel class of fluorescent molecular dyes
within the field of molecular biology and medicine. The spectral information from
CPs could be useful to gain more information regarding the molecular details of the
biological process and pathological events underlying a wide range of diseases,
such as the protein aggregation diseases. However, there is still a great extent of
basic research that must be performed to fully understand and properly utilize the
CP-based technique for studying biological events.
One attractive possibility is to develop CPs that can be used for in vivo imaging
of protein aggregates. In this regard, the synthesis of appropriately functionalized
CPs that are able to cross the blood-brain barrier (BBB) has been exemplified [ 36 ].
Such dyes can be utilized in powerful multi-photon imaging applications as previ-
ously reported CPs have been shown to have an excellent cross-section area
compared with small fluorescent dyes, making these molecules suitable for multi-
photon applications [ 33 , 37 ].
A novel thiophene-based molecular scaffold that could be used for optical
in vivo imaging of protein aggregates was recently reported by ˚ slund et al. [ 36 ].
This chemically defined anionic pentameric thiophene derivative, p-FTAA (Fig. 21a ),
could be utilized for direct in vivo detection of A deposit in the brain of a transgenic

mouse model with AD pathology. The deposits were easily visualized by two-photon

b