Binding of Polythiophenes to Amyloids: Structural Mapping of the Pharmacophore.
ACS Chem Neurosci
; 9(3): 475-481, 2018 03 21.
Article
em En
| MEDLINE
| ID: mdl-29178774
ABSTRACT
Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates. We clarify the binding site and mode of two different polythiophenes to fibrils of the prion domain of the HET-s protein by solid-state NMR and correlate these findings with their fluorescence properties. We demonstrate how amyloid dyes recognize distinct binding sites with specific topological features. Regularly spaced surface charge patterns and well-accessible grooves on the fibril surface define the pharmacophore of the amyloid, which in turn determines the binding mode and fluorescence wavelength of the polythiophene.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Tiofenos
/
Sítios de Ligação
/
Príons
/
Fluorescência
/
Amiloide
Limite:
Humans
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Suíça