The synthesis of (E)-2-cyano-3-(5-piperidin-1-yl-2,2-bithien-5-yl)acrylic acid, a novel amyloid aggregation fluorescent probe, is reported. This new probe is able to monitor soluble oligomeric aggregates after 24 h, at which time Thioflavin T emission, commonly used to monitor amyloid fibril formation, remains unchanged. Atomic force microscopy, native polyacrylamide gel electrophoresis, and dynamic light scattering confirm that the earlier stages of aggregation are prefibrillar oligomeric species not possessing the amyloid structure. This new molecular scaffold expands the toolbox of fluorescent probes for the identification of prefibrillar oligomers, which is needed in studies aimed at the early detection of the soluble toxic aggregates that characterize the so-called protein misfolding diseases.

(E)-2-Cyano-3-(5 alpha-piperidin-1-yl-2,2 alpha-bithien-5-yl)acrylic Acid: A Fluorescent Probe for Detecting Prefibrillar Oligomers

Attanasio, F
Co-primo
;
Bonaccorso, C
Co-primo
;
Bellia, F;Fortuna, CG;Musumarra, G
;
Pignataro, B;Rizzarelli, E
2013

Abstract

The synthesis of (E)-2-cyano-3-(5-piperidin-1-yl-2,2-bithien-5-yl)acrylic acid, a novel amyloid aggregation fluorescent probe, is reported. This new probe is able to monitor soluble oligomeric aggregates after 24 h, at which time Thioflavin T emission, commonly used to monitor amyloid fibril formation, remains unchanged. Atomic force microscopy, native polyacrylamide gel electrophoresis, and dynamic light scattering confirm that the earlier stages of aggregation are prefibrillar oligomeric species not possessing the amyloid structure. This new molecular scaffold expands the toolbox of fluorescent probes for the identification of prefibrillar oligomers, which is needed in studies aimed at the early detection of the soluble toxic aggregates that characterize the so-called protein misfolding diseases.
Heterocycles
Aggregation
Atomic force microscopy
Electrophoresis
Fluorescent probes
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/541740
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 5
social impact