Distinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene-Based Ligands to Distinguish Beta-Amyloid or Tau Polymorphic Aggregates
2015 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, no 25, 9072-9082 p.Article in journal (Refereed) Published
The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the existence of distinct aggregated morphotypes has been suggested to explain the heterogeneous phenotype reported for these diseases. Thus, the development of molecular probes able to distinguish such morphotypes is essential. We report an anionic tetrameric oligothiophene compound that can be utilized for spectral assignment of different morphotypes of -amyloid or tau aggregates present in transgenic mice at distinct ages. The ability of the ligand to spectrally distinguish between the aggregated morphotypes was reduced when the spacing between the anionic substituents along the conjugated thiophene backbone was altered, which verified that specific molecular interactions between the ligand and the protein aggregate are necessary to detect aggregate polymorphism. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between different morphotypes of protein aggregates.
Place, publisher, year, edition, pages
Wiley-VCH Verlag , 2015. Vol. 21, no 25, 9072-9082 p.
aggregates; Alzheimers disease; fluorescence; luminescent conjugated oligothiophenes; proteins
IdentifiersURN: urn:nbn:se:liu:diva-120041DOI: 10.1002/chem.201500556ISI: 000355762900019PubMedID: 26013403OAI: oai:DiVA.org:liu-120041DiVA: diva2:840016
Funding Agencies|Swedish Foundation for Strategic Research; Swedish Alzheimer Foundation; European Research Council Starting Independent Researcher Grant (MUMID)2015-07-062015-07-062015-09-03