TY - JOUR
T1 - (E)-2-Cyano-3-(5′-piperidin-1-yl-2,2′-bithien-5-yl)acrylic acid
T2 - A fluorescent probe for detecting prefibrillar oligomers
AU - Attanasio, Francesco
AU - Bonaccorso, Carmela
AU - Bellia, Francesco
AU - Cataldo, Sebastiano
AU - Fortuna, Cosimo G.
AU - Musumarra, Giuseppe
AU - Pignataro, Bruno
AU - Rizzarelli, Enrico
PY - 2013/6
Y1 - 2013/6
N2 - 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′-piperidin-1- yl-2,2′-bithien-5-yl)acrylic acid (p-TTCNAc) can be conveniently used as a fluorescent probe to identify prefibrillar oligomers of hen egg white lysozyme not detected by Thioflavin-T (ThT).
AB - 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′-piperidin-1- yl-2,2′-bithien-5-yl)acrylic acid (p-TTCNAc) can be conveniently used as a fluorescent probe to identify prefibrillar oligomers of hen egg white lysozyme not detected by Thioflavin-T (ThT).
KW - Aggregation
KW - Atomic force microscopy
KW - Electrophoresis
KW - Fluorescent probes
KW - Heterocycles
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U2 - 10.1002/ejoc.201300241
DO - 10.1002/ejoc.201300241
M3 - Article
AN - SCOPUS:84879205787
SP - 3635
EP - 3639
JO - Justus Liebigs Annalen der Chemie
JF - Justus Liebigs Annalen der Chemie
SN - 0075-4617
IS - 18
ER -