The structural basis for optimal performance of oligothiophene-based fluorescent amyloid ligands: conformational flexibility is essential for spectral assignment of a diversity of protein aggregates.
Chemistry
; 19(31): 10179-92, 2013 Jul 29.
Article
em En
| MEDLINE
| ID: mdl-23780508
ABSTRACT
Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as thioflavinâ
T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aß aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aß and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by 1)â
replacing thiophene units with selenophene or phenylene moieties, or 2)â
alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of disease-associated protein aggregates.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiofenos
/
Proteínas
/
Corantes Fluorescentes
/
Amiloide
Limite:
Animals
Idioma:
En
Revista:
Chemistry
Ano de publicação:
2013
Tipo de documento:
Article