首页 | 本学科首页   官方微博 | 高级检索  
     检索      


Distinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene‐Based Ligands to Distinguish β‐Amyloid or Tau Polymorphic Aggregates
Authors:Dr Therése Klingstedt  Dr Hamid Shirani  Jasmin Mahler  Dr Bettina M Wegenast‐Braun  Dr Sofie Nyström  Dr Michel Goedert  Prof Mathias Jucker  Dr K Peter R Nilsson
Institution:1. Department of Chemistry, Link?ping University, SE‐581 83 Link?ping (Sweden);2. Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen (Germany);3. DZNE, German Center for Neurodegenerative Diseases, Tübingen (Germany);4. MRC Laboratory of Molecular Biology, Cambridge (United Kingdom)
Abstract: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 β‐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.
Keywords:aggregates  Alzheimer’  s disease  fluorescence  luminescent conjugated oligothiophenes  proteins
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号